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ISSN : 1225-0171(Print)
ISSN : 2287-545X(Online)
Korean Journal of Applied Entomology Vol.61 No.1(Special Issue) pp.91-100

Osmoregulatory Physiology in Ixodidae Ticks: An Alternative Target for Management of Tick

Paulina Maldonado-Ruiz L., Donghun Kim1*, Yoonseong Park**
Department of Entomology, Kansas State University, Manhattan, KS 66506, USA
1Department of Vector Entomology, Kyungpook National University, Sangju 37224, Korea
January 10, 2022 February 2, 2022 February 8, 2022


Ticks are the arthropod vector capable of transmitting diverse pathogens, which include bacteria, viruses, protozoan and fungi. Ticks are able to survive under stressful environmental conditions. One of evolutionary outcomes of these obligatory hematophagous arthropods is the survival for extended periods of time without a blood meal during off-host periods. Water conservation biology and heat tolerance have allowed ticks to thrive even under high temperatures and low relative humidity, thus they have become highly successful arthropods as they are distributed globally. Tick osmoregulatory physiology is a complex mechanism, which involves multiple osmoregulatory organs (salivary glands, Malpighian tubules, hindgut and synganglion) for the acquisition and excretion of water and ions. Blood feeding and water vapor uptake have been early reported as the primary passages for ixodid tick to acquire water. Recently, we have learned that ticks can actively drink environmental water allowing hydration. The acquired water can be traced to the salivary glands (type I acini) and the midgut diverticula. This opens new avenues for tick management through the delivery of toxic agents into their drinking water, in addition to an alternative strategy for the study of tick physiology. Here we address the osmoregulatory physiology in the ixodid ticks as a potential target physiological mechanism for tick control. We discuss the implications of water drinking behavior for tick control through the delivery of toxic agents and discuss the dermal excretion physiology as an additional pathway to induce tick dehydration and tick death.

진드기의 수분조절 생리와 진드기 방제전략

말도나도-루이즈 폴리나, 김 동흔1*, 박 윤성**
캔자스주립대학교 곤충학과
1경북대학교 질병매개곤충학과


진드기는 박테리아, 바이러스, 원생동물 및 균류를 포함한 다양한 병원체를 전달할 수 있는 감염병매개체이다. 진드기는 불리한 환경조건에 서도 생존할 수 있는 능력이 있으며, 흡혈이 필수적인 절지동물의 진화적 산물로써 비흡혈 기간이 장기간 지속되는 경우에도 생존이 가능하다. 특 히, 높은 온도와 낮은 습도 환경에서도 견딜 수 있는 수분 조절 메커니즘과 내열성의 생리적 특징은 진드기가 전 세계적으로 분포하도록 한 중요한 요인이다. 진드기의 침샘, 말피기관, 후장 그리고 뇌를 포함하는 여러 기관이 관여하는 물과 이온의 획득 및 배출은 복합적인 메커니즘에 의해 조절 된다. 진드기가 수분을 확보하는 주요 경로는 흡혈과정 또는 공기 중 수증기를 직접 포집하는 방식이며, 이와 더불어 진드기가 자연조건에서 맺힌 물방울을 직접 마시며 수분을 보충한다는 것이 최근 본 연구진의 연구를 통해 밝혀졌다. 물방울에서 획득된 수분은 진드기 침샘의 포도상 부위(유형 I) 또는 중장을 통해 체내로 흡수된다는 것이 형광물질 추적을 통해 확인되었다. 이 연구 결과는 진드기 방제 및 병원체 전파 억제를 위한 전략 개발에 새로운 방향을 제시하였다. 본 종설에서는 진드기 방제를 위한 잠재적 표적인 진드기의 수분조절 및 표피 배설의 생리적 메커니즘을 종합적으로 다 룬다.

    Ticks: Ixodidae

    Ticks are obligate blood-feeding ectoparasites and one of the most prominent arthropods harboring pathogens worldwide (De la Fuente et al., 2008;Jongejan and Uilenberg, 2004). In the United States, ticks are the number one arthropod vector of animal or human diseases (CDC, 2018;Dantas-Torres et al., 2012;Mullen and Durden, 2002;WHO, 2014;Sonenshine and Roe, 2013b). Ticks belong to the Order Metastigmata (Ixodida), which includes three families Ixodidae (hard ticks), Argasidae (soft ticks), and Nuttalliellidae, containing the species of human and veterinary importance. The family Ixodidae contains the main vector species, comprising more than 700 species (Guglielmone et al., 2010;Mullen and Durden, 2002;Sonenshine and Roe, 2013a). Ixodidae ticks are subdivided into two groups: Prostriata, containing one genus (Ixodes) and Metastriata containing 11 genera, which include Amblyomma, Dermacentor, Hemaphysalis, and Rhipicephalus (Sonenshine and Roe, 2013a).

    All ticks are required to feed on a host in order to molt into the next stage (Sonenshine, 1991a), often allowing them to explore multiple hosts throughout their lifetime. Based on the lifestyle, ticks can be further divided into one-host, two-host or three-host ticks (Sonenshine and Roe, 2013a), although the majority of hard ticks fall under the three-host category. In the three-host life cycle, the ticks are required to feed on three different hosts (or three different attachments) in order to complete their life cycle and one single female can lay several thousands of eggs at once; the maximum record being Amblyomma variegatum with 36,206 eggs laid (Dipeolu and Ogunji, 1980). The life cycle of a hard tick can last from several months to multiple years including off-host state, during which their unique osmoregulatory physiology is required to survive under harsh environmental conditions. Hard ticks ingest a large amount of blood during a single blood meal, however it is estimated that they spend over 98% of their lifetime at off-host state (Sonenshine, 1991a;Sonenshine and Roe, 2013a). Therefore, tick survival is largely dependent on the environmental conditions, which include fluctuating temperatures and relative humidities (RH) (Needham and Teel, 1986). Consequently, tick success largely depends on their ability to maintain water balance in the environment with low RH (Needham and Teel, 1986;Norval, 1977).

    Osmoregulation in Insects and Other Bloodfeeding Arthropods

    Water is the basis of life as it makes up to 65 to 90% of all living organisms. All living organisms need to maintain the ideal concentration of ions or electrolytes within the cell for proper cellular functions. At the organismal level, gain of water requires uptake of dietary water while water loss occurs through the integument by evaporation and through the excretory system in the processes of eliminating metabolic wastes. Arthropods, including insects and arachnids, are especially susceptible to dehydration due to their small size and large surface-to-volume ratio compared to other animals. Their cuticle covered with a wax layer and other osmoregulatory mechanisms allow a large number of species withstanding the aridest environments (Berridge, 1970). When subjected to desiccation, the fruit fly (Drosophila melanogaster) can maintain a constant hemolymph osmolarity even after reducing their hemolymph volume down to below 25% (Albers and Bradley, 2004). Hematophagous arthropods, such as the kissing bug, the bed bug, fleas, and some ticks, have complicated ion regulation mechanisms to maintain water homeostasis during the blood meal (Benoit and Denlinger, 2010;Sonenshine, 1991b;Thiemann et al., 2003). Initial studies in the kissing bug (Rhodnius prolixus) and mosquitoes showed that the blood meal caused significant changes in the physiology of these arthropods. The blood meal provides an excess of Na+ and Cl- ions, which need to be quickly eliminated from the body, leading to post-meal diuresis in blood-feeding insects (Coast, 2009;Orchard et al., 2021;Stobbart, 1977). In the case of ticks, the long duration of blood-feeding, up to more than a week of feeding, requires a more complex process including the gene regulations depending on the feeding phases. In addition, ticks rely heavily on their ability to absorb water from the environment without a nutritious diet during their long off-host periods, which indicates that an intricate process of tick water osmoregulatory is in place to survive prolonged periods of time without a blood meal.

    Water Homeostasis in The Ixodid Tick

    Ticks, like many arthropods, are at constant threat of evaporative loss of water due to their small size. Water loss through the integument is generally well prevented by the integument sclerotized with a cuticle rich in wax. However, other imminent water losses naturally also occur through hindgut excretion, salivation (Kim et al., 2016), and dermal secretion.

    Water uptake

    Ticks have the capability to uptake water from water vapor. Water vapor uptake directly depends on the Critical Equilibrium Activity (CEA), which is the minimum RH at which ticks can passively uptake water and maintain water homeostasis (Sauer and Hair, 1971;Sonenshine, 1991b;Wharton and Richards, 1978). In most ixodid ticks, the CEA is close to 90% RH (Wharton and Richards, 1978). In A. americanum, water vapor uptake occurs between 85% and 93% RH and accounts for up to 77% of the water uptake (Freda and Needham, 1984) in the experimental conditions. Water vapor uptake was first reported in A. variegatum with the mouthparts as the main route (Rudolph and Knulle, 1974). Ticks secrete hygroscopic saliva, during periods of dehydration, which is rich in chloride, potassium, and sodium ions (Fig. 1A) (Hsu and Sauer, 1974;Needham and Teel, 1986). This high ionic saliva then captures water vapor from the environment, and it is later ingested by the tick (Needham and Teel, 1986) (Fig. 1B). Although the ability of ticks to maintain water homeostasis has been of great interest in the last several decades, a better understanding of tick success in water regulation will potentially provide the tools for tick control.

    It has been demonstrated that some species of ticks can actively drink water voluntarily to maintain water balance during off-host state. Water drinking behavior was observed for several Rhipicephalus species, D. nuttalli, A. hebraeum, and larvae of A. americanum (Londt and Whitehead, 1972;Splisteser and Tyron, 1986;Wilkinson, 1953). In contrast, some studies reported no water drinking behavior in Ixodes ricinus, D. marginatus, and D. reticulatus (Kahl and Alidousti, 1997;Lees, 1946;Meyer-Konig et al., 2001). While A. americanum and other metastriate ticks are generally directly drinking water (Fig. 1C) (Maldonado-Ruiz et al., 2020), prostriate ticks have a general tendency for avoidance to touch the water. However, it has been observed that a prostriate tick, Ixodes scapularis, approaches and touches water droplets and occasionally insert the hypostome (mouthparts) and drink water (5% of ticks tested) (Fig. 1D) (Kim et al., 2017). Other studies reported an increased weight gain in ticks, which was believed to occur not by the direct ingestion through the mouthpart (Knulle and Devine, 1972;Lees, 1948), but by being in physical contact with water droplets. These studies imply that further observations with varied conditions, such as the geographically different strains and varied environmental conditions, are required for a solid conclusion. Ingested water through the mouthparts is later observed in the internal tick organs, type I acini of salivary glands (Fig. 1E and 1F) and midgut, and transported into the hemolymph based on a study tracing the fluorescence dye in the ingested water (Kim et al., 2017). Tick-specific mechanisms of water uptake likely offer a new target system that could be utilized for the development of a novel tick control strategy. In addition, direct uptake of water in ticks is a potential route for delivering tick-specific toxic reagents, as we previously demonstrated (Maldonado-Ruiz et al., 2020). It has been shown that ticks are able to ingest different bacteria through voluntary drinking, and such bacteria can be later recovered from the tick gut. In addition, 100% tick mortality has been achieved in A. americanum, upon ingestion of phosphate-rich salt solutions by voluntary drinking. High levels of excretions through the hindgut of dying ticks were observed after ingestion of phosphate-rich salt solutions, suggesting the mortality was caused by excessive dehydration caused by the increased excretion. Nonetheless, 60% tick mortality was also achieved through voluntary drinking of water containing Pseudomonas aeruginosa, which is an opportunistic pathogen (Maldonado-Ruiz et al., 2020) in A. americanum. While it is unlikely that this bacterium can be used as a control strategy, this demonstrates mortality through voluntary ingestions in the unfed tick can be achieved and that this strategy can also be used for delivery of other tick-specific toxic compounds.

    Main osmoregulatory organs and the control of water physiology

    Excretory mechanisms in the ixodid ticks are similar to those observed in insects, but significantly different in the neural and hormonal components involved in the process (Sonenshine and Roe, 2013a). In hard ticks, the salivary glands (Fig. 1E, in blue), Malpighian tubules (Fig. 1E, in yellow), and hindgut (Fig. 1E, in green) are the main osmoregulatory organs. The excretory organs, hindgut and Malpighian tubules, are believed to be controlled by the brain of the tick (synganglion) (Fig. 1E, in pink) (Šimo and Park, 2014), while the mechanisms of tick salivary secretion are not yet fully understood (Kim et al., 2019).

    Salivary glands

    The salivary glands of ticks are the largest pair of glands in the Ixodid tick’s body, and are responsible for maintaining water balance in both off-host and on-host ticks (Sonenshine and Roe, 2013a;Sonenshine, 1991a). There are three types of acini (alveoli) in the female tick (Type I, II and III) (Fig. 1F) and 4 types in males (I-IV). Type I acini are agranular and attached directly to the anterior part (or proximal region) of the salivary duct. They have been associated primarily with off-host osmoregulation through the absorption of water after hygroscopic saliva is secreted during dehydration (Kim et al., 2017;Kim et al., 2019;Sonenshine, 1991a, b;Sonenshine and Roe, 2013a;Walker et al., 1985). Type II and type III acini are granular and more complex in structure, which shows drastic anatomical changes during feeding (Sonenshine and Roe, 2013a;Sonenshine, 1991a;Walker et al., 1985). Type II and type III acini have been associated primarily with water and ion excretion during feeding periods in addition to the production and secretion of bioactive molecules into their host (Kaufman and Phillips, 1973;Kim et al., 2019;Perner et al., 2018;Sonenshine and Roe, 2013a;Valenzuela et al., 2002).

    It has been reported that tick salivary secretion is regulated through neuronal and hormonal signals (Sauer et al., 2000). The main regulator of the excretion and the influx of fluid into the lumens of the type II and III acini is dopamine which acts as a paracrine/autocrine hormone (Kim et al., 2014;Kim et al., 2019;Sauer et al., 2000). Two different dopamine receptors have been identified as the downstream physiological targets in type II and III acini: D1 receptor for the water-solute influx and InvD1L for the expulsion of water solute via pumping/gating (Šimo et al., 2011;Šimo et al., 2014). Experiments by heterologous receptor expression suggested that D1 is mainly coupled to cAMP, while InvD1L to Ca2+ elevation in the downstream signaling pathway (Sauer et al., 2000;Šimo et al., 2011;Šimo et al., 2014). As the upstream signal in the control of salivary glands, a number of neuropeptidergic projections reaching to the salivary glands have been described: SIFamide, Elevenin, and MIP (myoinhibitory peptide) (Šimo and Park, 2014). The locations of the neuropeptidergic varicosities and the receptors implicated that their modulatory functions for control of secretion and also for the feedback control of autocrine dopamine in the salivary glands. Overall, the salivary glands, playing a vital role in osmoregulatory processes in addition to contributing to vector competence as tick saliva is an important factor in pathogen transmission (Nuttall, 2019a, b;Valenzuela et al., 2002), are tightly controlled by neural and hormonal components for the activities.

    Hindgut and Malpighian tubules

    Malpighian tubules and hindgut are located at the terminal end of the alimentary canal with the major function as excretion of metabolic wastes (Sonenshine and Roe, 2013a;Sonenshine, 1991a). A pair of Malpighian tubules, long tubes with the dead ends, arises at the midgut-hindgut junction. The hindgut is in direct contact with the anus and wrapped by longitudinal and cross muscles. A number of neural projections innervate the hindgut, which are neurons immunoreactive to SIFamide and MIP. The neuropeptide SIFamide stimulates hindgut motility, which was antagonized by MIP in Ixodes scapularis, (Šimo and Park, 2014).

    It has been reported that K+ is the major solute in the excretion being defecated through the hindgut, while Na+ is the major solute in the saliva during feeding periods (Kaufman and Phillips, 1973). In insects, the primary role of Malpighian tubules is the elimination of nitrogenous waste in the form of uric acid by the formation of hyperosmotic urine through the transport of K+ from the hemolymph into the tubular lumen that is energized by V-ATPase and the transport of Na+ out of the cell through Na/K-ATPase (Sonenshine and Roe, 2013a). Tick Malpighian tubules are also known to be the major site for the formation of nitrogenous waste in the form of guanine-rich excreta (Hamdy and Sidrak, 1982;Maddrell and O'Donnell, 1992;Sonenshine, 2013). The mechanism controlling the tick Malpighian tubules has not been yet studied, while insect Malpighian tubule has been intensively studied for the hormonal components and the mechanisms of V-ATPase mediated fluid transport in formation and secretion of the primary urine (Beyenbach, 2003;Maddrell and O'Donnell, 1992).

    In other blood-feeding insects such as the kissing bug, potassium urate is formed in the Malpighian tubules, and further urine concentration is achieved in the rectal sac through the reabsorption of water before excretion (Pant, 1988;Sonenshine and Roe, 2013a;Wigglesworth, 1931). In ixodid ticks, hindgut excretion is primarily for the removal of potassiumrich excreta. Guanine has been suggested as the main nitrogenous component of excretion in addition to haematin and undigested blood. However, little is known about the molecular components regulating hindgut activity (Sonenshine and Roe, 2013a). Although imminent water losses occur through the cuticle, which accounts for a significant amount of water loss, natural water losses through Malpighian tubules and hindgut in the process of excretion of waste is also likely a significant as the target of osmoregulatory disruptor.

    Dermal secretion through the cuticle

    The phenomenon of dermal excretion through the cuticle in Ixodid ticks has long been observed, although the osmoregulatory implications of the physiology have not been investigated. Dermal secretion constitutes a significant amount of water, at least 4% of fluid from the body weight within seconds (Yoder et al., 2009), and it is known to occur through the numerous dermal glands located on the tick’s epidermal cell layer. Four different types of dermal glands and pore structures have been described in ticks, although their functions are yet controversial (Sonenshine and Roe, 2013a), and their morphology appears to vary in structure depending on the tick species. This characterization is based exclusively on the anatomy of the pore structures being non-setal associated with no innervation. The dermal glands are classified into four structural categories: sensilla auriformia, sensilla sagittiformia, sensilla hastiformia, and sensilla latcniformia, the latter being absent in adult ticks.

    Sensilla auriformia in R. appendiculatus was thought to be a sensory organ proprioceptor (Walker et al., 2014), while other studies defined it as a dermal gland (Pavis et al., 1994;Yoder et al., 2009). Sensilla hastiformia, also known as type I gland or small gland (Fig. 2A), is found in alloscutum and scutum of both metastriate and prostriate ticks in all stages, but appears to be underdeveloped in the non-fed stage (Walker et al., 1996). While scnsilla sagittiformia, also known as type II gland or large wax gland (Fig. 2B), are exclusive to Metastriate ticks and have been found in the alloscutum, edge of scutum, and anal plates of fed Rhipicephalus (Yoder et al., 2009). Type II glands are known to produce secretions in ticks which are in engorging stage but also in questing (non-fed) ticks (Walker et al., 1996;Walker et al., 2014). The primary role of type I and type II glands is assumed to secret defensive compounds against predators and pathogens. These chemical components of the secretion include squalene and other unidentified compounds, which can be externalized through canal (pore) openings on the cuticle surface (Hackman and Filshie, 1982;Pavis et al., 1994), some of which are suggested to be acting as allomones against predatory ants. However, the functional studies of the components of dermal secretions has not been successful in showing the clear biological activities despite the predictions of the hypothetical functions (Yoder et al., 1993). The dermal secretion has been reported to be triggered through mechanical stimulation (Sonenshine and Roe, 2013a;Walker et al., 1996) and the mechanically induced secretion provided heat tolerance in R. sanguineus ticks (Yoder et al., 2009). Our recent study demonstrated the role of the dermal secretion in thermoregulation and osmoregulation. With the significant amount of water being secreted through this mechanism, it provides a promising target physiology for tick control.

    Thermoregulation and tick dermal secretion

    Higher animals rely on thermoregulation to maintain the homeostasis of metabolic functions (Crompton et al., 1978;Terrien et al., 2011). Thermoregulation in arthropods has been observed during their blood meal in order to prevent the heat stress caused by the warm ingested blood (Benoit et al., 2019). Different thermoregulatory strategies have been observed in several blood-feeding arthropods. Mosquitoes retain drops of urine in the abdomen which provides temperature decreases as the urine evaporates (Lahondère and Lazzari, 2012), while the kissing bug dissipates heat from the head during the blood meal (Lahondère et al., 2017). Arthropod thermoregulation has been broadly studied in hematophagous arthropods during the blood ingestion: however, studies on evaporative cooling in arthropods including ticks during the non-feeding periods is limited.

    Dermal secretion of hard ticks has primarily been associated with defense mechanisms against pathogens and predators such as the predatory ant (Pavis et al., 1994;Yoder et al., 1993). Our research group has recently suggested that this secretion can also serve as a thermoregulatory strategy during the off-host periods. Heat stimulation induced dermal secretion of the unfed lone star tick A. americanum, followed by a rapid cooling of the body temperature. The secretion can be observed at temperatures as low as 35°C (similar temperatures during summer in the tick microhabitat) and at least 60% of consistently responding in different trials (Fig. 2C and 2D). Serotonin and Na+/ K+-ATPase have been proposed as the main regulators of dermal secretion. Injection of serotonin (1mM in 10nl) induced dermal secretion, which was inhibited by pre-injection with ouabain (a Na+/K+-ATPase blocker) (Fig. 2E). Previous reports show that the secretion of salivary glands and hindgut is controlled by the neural and hormonal controllers (Kim et al., 2019;Šimo and Park, 2014). Our recent findings on dermal secretion molecular controllers also suggest that the response is controlled by neural/hormonal mechanisms. The proposed thermoregulatory function of the dermal secretion is probably stemmed from the fact that the secretion accounts for an excessive loss of fluid (4.1% of body weight). In addition to the rapid response in secretion, which suggests it may be triggered by heat rather than just as a defense mechanism caused by disturbance. Thus, dermal secretory physiology likely occurs in the field when ticks are not able to avoid high temperatures, as suggested to occur in hot summer days periods .

    Novel Strategy to Control Tick by Targeting the Vulnerable Osmoregulatory Physiology

    In recent years, the research in ticks has significantly increased; however, the knowledge we currently have is yet limited in comparison to other blood-feeding arthropods such as mosquitoes. Control of ticks in the field is heavily relying upon the use of conventional insecticides and acaricides. Although the method of application and the formulation of toxic chemicals in tick control have been improved, new classes of chemicals for controlling ticks are urgently in need since ticks have developed acaricide resistance (Abbas et al., 2014;Coles and Dryden, 2014). The safety and environmental issues became more important in the development of tick control measures. Rational design of the tools and methods for tick control can be made based on understanding tick biology and physiology, and as such, targeting the vulnerable osmoregulatory physiology proposes a good target for management.

    In metastriate ticks, water drinking behavior is common and has a significant impact on tick survival. Water drinking behavior is an important part of water conservation physiology and as such, it is a promising target for tick control. The delivery of toxic agents which leads to tick mortality, as in the case of phosphate-rich solution through drinking water, is a promising proposal for management and adds new avenues for tick research. In addition, the ingestion of bacteria, which can be later traced to the tick midgut, provides an opportunity for elucidating tick vector competence if certain bacteria can successfully colonize the tick gut.

    Recent findings suggest that dermal secretion provides evaporative cooling, which could be occurring in nature. This could be a factor contributing to their extended survival rates and habitat expansions to geographical areas with hot temperatures. Dermal secretion involved in osmoregulatory physiology and thermoregulation may offer a vulnerable tick physiology that can be targeted for the development of a novel tick control strategy. Based on the prediction of the direct action of serotonin on the dermal gland, a candidate serotonin receptor (Aame5- HT1A) was recently identified from A. americanum (our unpublished data). Aame5-HT1A was found only in epidermalenriched carcass among the four different tissues including carcass, midgut, hindgut, and Malpighian tubules. The Aame5- HT1A orthologue was previously identified in R. microplus (the southern cattle tick) (Chen et al., 2004), but without its known function. The identification of potential agonistic or antagonistic compounds of these osmoregulatory and thermoregulatory controller molecules might provide an additional target for management.


    Here we propose the use of new tick control strategies, which primarily target the vulnerable osmoregulatory physiology in Ixodidae ticks. The exploitation of tick water drinking behavior for the delivery of toxic agents (phosphates or bacteria), can induce tick mortality by dehydration or disruption of tick bacterial homeostasis.

    The knowledge we have gained over the recent years about neuronal and hormonal control of the main tick osmoregulatory organs, combined with voluntary ingestion of toxic cagents, may improve our previous results by accelerating tick mortality. Similarly, through the delivery of osmoregulatory modulator molecules, blocking rehydration and/or inducing dehydration may accelerate tick death if combined with the delivery of other toxic agents. In this environmentally friendly manner, a tick-specific management strategy may be further developed and proposes a promising management strategy, alternative to pesticides, if applied in the field for tick control.


    DK was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1G1A1100559) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1I1A3055954). YP was supported by NIH grants NIH-NIAID R21 AI135457 and AI163423, 1S10OD026726 and USDA-NIFA, GRANT- 13066347. Contribution number 21-xxx-J from the Kansas Agricultural Experiment Station.


    Schematic representation of water uptake in metastriate ticks and main osmoregulatory organs. (A) Representation of vapor uptake through the secretion of hygroscopic saliva (a1 in yellow) in low relative humidity (RH) and (B) hyperosmolar saliva capturing water molecules from the environment (blue) for rehydration. (C) Voluntary water drinking behavior in unfed A. americanum (D) and I. scapularis (Kim et al., 2017). (E) Anatomy of hard ticks, showing the major internal organs. salivary glands (blue) and (c1) type I, II and type III acini, synganglion (pink), hindgut (green), and Malpighian tubules (yellow tubular ducts) and (F) the different types of salivary gland acini in hard ticks (modified from Kim et al., 2017).


    Dermal glands in A. americanum and dermal secretion. (A) Compound microscope image from tick sections stained with methylene blue and eosin (Magenta square shows the dermal gland type I and the pore and (B) type II dermal gland and pore outlined by a blue square. (C) Dermal secretion in A. americanum female adult after hot environment simulation (incubator temperature 50°C). (D) Inset of C. (E) Response of dermal secretion after injection with 10 nl of serotonin (20 minutes after pre-injection with Ouabain (Na+-/K+--ATPase blocker), or water (controls)).


    1. Abbas, R.Z. , Zaman, M.A. , Colwell, D.D. , Gilleard, J. , Iqbal, Z. ,2014. Acaricide resistance in cattle ticks and approaches to its management: The state of play. Vet. Parasitol. 203, 6-20.
    2. Albers, M.A. , Bradley, T.J. ,2004. Osmotic regulation in adult Drosophila melanogaster during dehydration and rehydration. J. Exp. Biol. 207, 2313-2321
    3. Benoit, J.B. , Denlinger, D.L. ,2010. Meeting the challenges of onhost and off-host water balance in blood-feeding arthropods. J. Insect. Physiol. 56, 1366-1376.
    4. Benoit, J.B. , Lazzari, C.R. , Denlinger, D.L. , Lahondère, C. ,2019. Thermoprotective adaptations are critical for arthropods feeding on warm-blooded hosts. Curr. Opin. Insect. Sci. 34, 7-11.
    5. Berridge, M.J. ,1970. Osmoregulation in terrestrial arthropods, in: Flokin, M. (Ed.), Chemical zoology V5: Arthropoda Part A, Part 1. Academic Press, New York, pp. 287-316.
    6. Beyenbach, K.W. ,2003. Transport mechanisms of diuresis in Malpighian tubules of insects. J. Exp. Biol. 206, 3845-3856.
    7. CDC,2018. Tickborne diseases in the United States: A reference manual for healthcare providers, 5 ed, (accessed on 20 December, 2020).
    8. Chen, A. , Holmes Sp Fau - Pietrantonio, P.V. , Pietrantonio, P.V. ,2004. Molecular cloning and functional expression of a serotonin receptor from the Southern cattle tick, Boophilus microplus (Acari: Ixodidae). Insect Mol Biol. 13, 45-54.
    9. Coast, G.M. ,2009. Neuroendocrine control of ionic homeostasis in blood-sucking insects. J. Exp. Biol. 212, 378-386.
    10. Coles, T.B. , Dryden, M.W. ,2014. Insecticide/acaricide resistance in fleas and ticks infesting dogs and cats. Parasites & Vectors 7, 8.
    11. Crompton, A.W. , Taylor, C.R. , Jagger, J.A. ,1978. Evolution of homeothermy in mammals. Nature 272, 333-336.
    12. Dantas-Torres, F. , Chomel, B.B. , Otranto, D. ,2012. Ticks and tickborne diseases: a one health perspective. Trends Parasitol. 28, 437-446.
    13. De la Fuente, J. , Estrada-Pena, A. , Venzal, J.M. , Kocan, K.M. , Sonenshine, D.E. ,2008. Overview: Ticks as vectors of pathogens that cause disease in humans and animals. Front. Biosci. 13, 6938-6946.
    14. Dipeolu, O.O. , Ogunji, F.O. ,1980. Laboratory studies on factors influencing the oviposition and eclosion patterns of Amblyomma vagieratum (Fabricius, 1794) females. Folia Parasitol. 27, 257-264.
    15. Freda, T.J. , Needham, G.R. ,1984. Water exchange kinetics of the long star tick Amblyomma americanum, in: Griffiths, D.A., Bowman, C.E. (Eds.) Acarology Vol.6, Horwood, Chichester, pp. 358-364.
    16. Guglielmone, A.A. , Robbins, R.G. , Apanaskevich, D.A. , Petney, T.N. , Estrada-Pena, A. , Horak, I.G. , Shao, R. , Barker, S.C. ,2010. The Argasidae, Ixodidae and Nuttalliellidae (Acari: Ixodida) of the world: a list of valid species names. Zootaxa 2528, 1-28.
    17. Hackman, R.H. , Filshie, B.K. 1982. The tick cuticle, Physiology of Ticks (Vol 1.). Pergamon Press, UK, pp. 1-42.
    18. Hamdy, B.H. , Sidrak, W. ,1982. Guanine biosynthesis in the Ticks (Acari) Dermacentor Andersoni (Ixodidae) and Argas (Persicargas) Arboreus (Argasidae): Fate of Labelled Guanine Precursors 1, 2. J. Med. Entomol. Suppl. 19, 569-572.
    19. Hsu, M.H. , and Sauer, J. R. ,1974. Sodium, Potassium, Chloride and water balance in the feeding lone star tick, Amblyomma americanum (Linneaus) (Acarina: Ixodidae). J. Kans. Entomol. Soc. 47, 536-537.
    20. Jongejan, F. , Uilenberg, G. ,2004. The global importance of ticks. Parasitology 129 Suppl, S3-14.
    21. Kahl, O. , Alidousti, I. ,1997. Bodies of liquid water as a source of water gain for Ixodes ricinus ticks (Acari: Ixodidae). Exp. Appl. Acarol. 21, 731-746.
    22. Kaufman, W.R. , Phillips, J.E. ,1973. Ion and water balance in the Ixodid tick Dermacentor Andersoni. I. Routes of Ion and Water Excretion. J. Exp. Biol. 58, 523-536.
    23. Kim, D. , Maldonado-Ruiz, P. , Zurek, L. , Park, Y. ,2017. Water absorption through salivary gland type I acini in the blacklegged tick, Ixodes scapularis. PeerJ 5, e3984.
    24. Kim, D. , Šimo, L. , Park, Y. ,2014. Orchestration of salivary secretion mediated by two different dopamine receptors in the blacklegged tick Ixodes scapularis. J. Exp. Biol. 217, 3656-3663.
    25. Kim, D. , Šimo, L. , Vancova, M. , Urban, J. , Park, Y. ,2019. Neural and endocrine regulation of osmoregulatory organs in tick: Recent discoveries and implications. Gen. Comp. Endocrinol. 278, 42-49.
    26. Kim, D. , Urban, J. , Boyle, D.L. , Park, Y. ,2016. Multiple functions of Na/K-ATPase in dopamine-induced salivation of the Blacklegged tick, Ixodes scapularis. Sci. Rep. 6, 21047.
    27. Knulle, W. , Devine, T.L. ,1972. Evidence for active and passive components of sorption of atmospheric water vapour by larvae of the tick Dermacentor variabilis. J. Insect. Physiol. 18, 1653-1664.
    28. Lahondère, C. , Insausti, T.C. , Paim, R.M.M. , Luan, X. , Belev, G. , Pereira, M.H. , Ianowski, J.P. , Lazzari, C.R. ,2017. Countercurrent heat exchange and thermoregulation during blood-feeding in kissing bugs. eLife 6, e26107.
    29. Lahondère, C. , Lazzari, C.R. ,2012. Mosquitoes cool down during blood feeding to avoid overheating. Curr. Biol. 22, 40-45.
    30. Lees, A.D. ,1946. The water balance in Ixodes ricinus L. and certain other species of ticks. Parasitology 37, 1-20.
    31. Lees, A.D. ,1948. Passive and active water exchange through the cuticle of ticks. Discuss. Faraday Soc. 3, 187-192.
    32. Londt, J.G. , Whitehead, G.B. ,1972. Ecological studies of larval ticks in South Africa (Acarina: Ixodidae). Parasitology 65, 469-490.
    33. Maddrell, S. , O'Donnell, M. ,1992. Insect Malpighian tubules: V-ATPase action in ion and fluid transport. J. Exp. Biol. 172, 417-429.
    34. Maldonado-Ruiz, L.P. , Park, Y. , Zurek, L. ,2020. Liquid water intake of the lone star tick, Amblyomma americanum: Implications for tick survival and management, Scientific Reports. p. 6000.
    35. Meyer-Konig, A. , Zahler, M. , Gothe, R. ,2001. Studies on survival and water balance of unfed adult Dermacentor marginatus and D. reticulatus ticks (Acari: Ixodidae). Exp. Appl. Acarol. 25, 993-1004.
    36. Mullen, G.R. , Durden, L.A. ,2002. Ticks (Ixodida), medical and veterinary entomology. Academic Press, Amsterdam, pp. 517-558.
    37. Needham, G.R. , Teel, P.D. ,1986. Water balance by ticks between bloodmeals, in: Sauer, J.R., Hair, J.A., (Eds.), Morphology, physiology and behavioral biology of ticks. Ellis Horwood Limited, Chinchester, England, pp. 100-151.
    38. Norval, R.A. ,1977. Studies on the ecology of the tick Amblyomma hebraeum Koch in the eastern Cape province of South Africa. II. Survival and development. J. Parasitol. 63, 740-747.
    39. Nuttall, P.A. ,2019a. Tick saliva and its role in pathogen transmission. Wien. Klin. Wochenschr. 2019, 1-12.
    40. Nuttall, P.A. ,2019b. Wonders of tick saliva. Ticks Tick Borne Dis. 10, 470-481.
    41. Orchard, I. , Leyria, J. , Al-Dailami, A. , Lange, A.B. ,2021. Fluid secretion by malpighian tubules of rhodnius prolixus: Neuroendocrine control with new insights from a transcriptome analysis. Front. Endocrinol. 12, 772487.
    42. WHO,2014. A global brief on vector-borne diseases. Tech. Rep.
    43. Pant, R. ,1988. Nitrogen excretion in insects. Proc. Indian Acad. Sci. (Anim. Sci). 97, 379-415.
    44. Pavis, C. , Mauleon, H.,Barre, N. , Maibeche, M. ,1994. Dermal gland secretions of tropical bont tick,Amblyomma variegatum (Acarina: Ixodidae): Biological activity on predators and pathogens. J. Chem. Ecol. 20, 1495-1503.
    45. Perner, J. , Kropáčkov á, S. , Kopáček, P. , Ribeiro, J.M.C. ,2018. Sialome diversity of ticks revealed by RNAseq of single tick salivary glands. PLoS. Negl. Trop. Dis. 12, 1-17.
    46. Rudolph, D. , Knulle, W. ,1974. Site and mechanism of water vapour uptake from the atmosphere in ixodid ticks. Nature 249, 84-85.
    47. Sauer, J.R. , Essenberg, R.C. , Bowman, A.S. ,2000. Salivary glands in ixodid ticks: control and mechanism of secretion. J. Insect. Physiol. 46, 1069-1078.
    48. Sauer, J.R. , Hair, J.A. ,1971. Water balance in the lone star tick (Acarina: Ixodidae): the effects of relative humidity and temperature on weight changes and total water content. J. Med. Entomol. 8, 479-485.
    49. Šimo, L. , Koči J. , Park, Y. ,2014. Invertebrate specific D1-like dopamine receptor in control of salivary glands in the blacklegged tick Ixodes scapularis. J. Comp. Neurol. 522, 2038-2052
    50. Šimo, L. , Koči, J. , Žitňan, D. , Park, Y. ,2011. Evidence for D1 dopamine receptor activation by a paracrine signal of dopamine in tick salivary glands. PLoS ONE 6, e16158.
    51. Šimo, L. , Park, Y. ,2014. Neuropeptidergic control of the hindgut in the black-legged tick Ixodes scapularis. Int. J. Parasitol. 44, 819-826.
    52. Sonenshine, D.E. ,1991a. Life cycles of ticks, in: Sonenshine, D.E., Roe, R.M. (Eds.), Biology of ticks, New York, pp. 51-66.
    53. Sonenshine, D.E. ,1991b. Water balance in non-feeding ticks, in: Sonenshine, R. (Ed.), In Biology of Ticks, New York, pp. 398-412.
    54. Sonenshine, D.E. ,2013. Excretion and water balance: hindgut, malpighian tubules and coxal glands, in: Sonenshine, D.E., Roe, R.M. (Eds.), Biology of ticks. Oxford University Press, New York, pp. 2016-2218.
    55. Sonenshine, D.E. , Roe, R.M. ,2013a. Biology of Ticks Volume 1. Oxford University Press, Incorporated, Cary, United States.
    56. Sonenshine, D.E. , Roe, R.M. ,2013b. Biology of Ticks Volume 2. Oxford University Press, Incorporated, Cary, United States.
    57. Splisteser, H. , Tyron, U. ,1986. Untersuchungen zu faunistischen besonderheiten und zur aktivitat von Dermacentor nuttalli in der Mongolischen Volksrepublik. Monatshefte für Veterinärmedizin 414, 126-128.
    58. Stobbart, R.H. ,1977. The control of the diuresis following a blood meal in females of the yellow fever mosquito Aedes aegypti (L). J. Exp. Biol. 69, 53-85.
    59. Terrien, J. , Perret, M. , Aujard, F. ,2011. Behavioral thermoregulation in mammals: a review. Front. Biosci. 16, 1428-1444.
    60. Thiemann, T. , Fielden, L.J. , Kelrick, M.I. ,2003. Water uptake in the cat flea Ctenocephalides felis (Pulicidae: Siphonaptera). J. Insect. Physiol. 49, 1085-1092.
    61. Valenzuela, J.G. , Francischetti, I.M.B. , Pham, V.M. , Garfield, M.K. , Mather, T.N. , Ribeiro, J.M.C. ,2002. Exploring the sialome of the tick Ixodes scapularis. J. Exp. Biol. 205, 2843-2864.
    62. Walker, A.R. , Fletcher, J.D. , Gill, H.S. ,1985. Structural and histochemical changes in the salivary glands of Rhipicephalus appendiculatus during feeding. Int. J. Parasitol. 15, 81-100.
    63. Walker, A.R. , Lloyd, C. , Mcguire, K. , Harrison, S.J. , Hamilton, J. ,1996. Integumental glands of the tick Rhipicephalus appendiculatus (Acari:Ixodidae) as potential producers of semiochemicals. J. Med. Entomol. 33 5, 743-759.
    64. Walker, A.R. , Lloyd, C.M. , McGuire, K. , Harrison, S.J. , Hamilton, J.G.C. ,2014. Integument and Sensillum Auriforme of the Opisthosoma of Rhipicephalus appendiculatus (Acari: Ixodidae). J. Med. Entomol. 33, 734-742.
    65. Wharton, G.W. , Richards, A.G. ,1978. Water vapor exchange kinetics in insects and acarines. Annu. Rev. Entomol. 23, 309-328.
    66. Wigglesworth, V.B. ,1931. The physiology of excretion In a bloodsucking insect; Rhodnius prolixus; (Hemiptera, Reduviidae). J. Exp. Biol. 8, 411.
    67. Wilkinson, P.R. ,1953. Observations on the sensory physiology and behaviour of larvae of the cattle tick, Boophilus Microplus (Can.) (Ixodidae). Aust. J. Zool. 1, 345-356.
    68. Yoder, J.A. , Benoit, J.B. , Bundy, M.R. , Hedges, B. Z. , Gribbins, K.M. ,2009. Functional morphology of secretion by the large wax glands (Sensilla sagittiformia) Involved in tick defense. Psyche J. Entom. 2009, 1-8.
    69. Yoder, J.A. , Hedges, B.Z. , Tank, J.L. , Benoit, J.B. ,2009. Dermal gland secretion improves the heat tolerance of the brown dog tick, Rhipicephalus sanguineus, allowing for their prolonged exposure to host body temperature. J. Therm. Biol. 34, 256-265.
    70. Yoder, J.A. , Pollack, R.J. , Spielman, A. ,1993. An ant-diversionary secretion of ticks: First demonstration of an acarine allomone. J. Insect. Physiol. 39, 429-435.