Tick modulation of host immunity: an important factor in pathogen transmission
Introduction
Disease-causing agents transmitted by blood-feeding arthropods are significant public health concerns[1]. In addition to the emergence of new diseases, many well-recognised vector-borne diseases are occurring more frequently and are increasing the range over which they occur. Many factors contribute to the emergence and re-emergence of arthropod-borne diseases: insecticide/acaricide resistance; drug resistance; economic and social factors; environmental change; and genetic changes in the vector-borne pathogens1, 2.
On a global basis, ticks are second only to mosquitoes as vectors of disease-causing agents to humans, and they are the most important arthropod transmitting pathogens to other animal species[3]. The public health importance of ticks is not diminishing. Furthermore, new tick-borne disease causing agents are being discovered. Lyme borreliosis, caused by Borrelia burgdorferi, occurs in regions with temperate climates, and it is the most frequently reported vector-borne disease in the United States[4]. In the United States, the vectors of B. burgdorferi are Ixodes scapularis in the east and midwest and Ixodes pacificus in the west[5]. In addition to B. burgdorferi, I. scapularis is a vector of the human pathogens: Babesia microti[6]; the causative agent of human granulocytic ehrlichiosis[7]; and a recently described encephalitis-like virus[8]. In addition, Ehrlichia chaffeensis, transmitted by Amblyomma americanum, causes human monocytic ehrlichiosis[7], which was described as a new species in 1991[9]. Furthermore, E. chaffeensis infections have been reported from Europe and Africa[7]. Throughout the world, it would be surprising if new emerging and re-emerging tick-borne diseases are not encountered in the coming years.
The tick is clearly not just a crawling hypodermic needle and syringe with regard to the transmission of tick-borne pathogens. Tick-transmitted infectious agents undergo developmental cycles within the vector. The microorganisms can express molecules during the vector phase that are not evident during infection of the mammalian host. The outer surface lipoprotein OspA is expressed by B. burgdorferi within the unfed tick, but it is down regulated upon initiation of blood-feeding[10]. As OspA expression is being reduced, expression of the lipoprotein OspC is being upregulated. Likewise, the 6.6 kDa outer membrane associated lipoprotein of B. burgdorferi is expressed during the tick phase of the spirochete life cycle[11]. Recently, Borrelia hermsii was shown to undergo phenotypic changes between the mammalian host and the tick vector, Ornithodoros hermsi[12]. Additional factors of great importance in tick feeding and pathogen transmission are the number and diversity of pharmacologically active molecules in tick saliva. Those activities include anti-coagulants; inhibitors of platelet aggregation; vasodilators; and suppressants of host immune defenses13, 14. Ticks, as well as blood-feeding arthropods in general, are indeed `smart pharmacologists'[13]. The factors of vector specific phenotype of tick-borne pathogens and the pharmacological activities of tick saliva change the way in which we think about and study tick-borne disease-causing agents. The vector environment and pharmacological properties of vector saliva establish the fact that the arthropod is not a passive partner in the vector–host–pathogen relationship.
This report focusses on the ability of ticks to modulate host immune responses and the potential consequences of that immunosuppression for pathogen transmission. Furthermore, the inhibition of the action of tick-derived host immunosuppressants might provide a powerful, novel, strategy for the control of tick-transmitted pathogens. Rather than targeting each individual tick-borne pathogen for vaccine development, develop a vector-blocking vaccine to those tick factors essential for successful transmission and establishment of disease-causing agents.
Section snippets
Immune responses to infestation
Due to the fact that ixodid ticks acquire a blood meal over a period of days, it is easy to understand how they induce host immune responses to salivary gland derived molecules[15]. Although not the topic of this report, short-term blood feeding insects induce host immune responses to their bites. Recent reviews have been published regarding host immunity to bugs, fleas and sucking lice[16], as well as mosquitoes and flies[17]. Indeed, ectoparasitic insects stimulate an array of host innate and
Modulation of host immunity
Disease-causing microorganisms, ranging from viruses to metazoan endoparasites, are able to suppress or deviate host innate and specific acquired immune responses39, 40, 41. Some of the immunomodulatory strategies employed include: impairing the function of antigen presenting cells; reducing T-lymphocyte function; suppressing and deviating cytokine production and action; diminishing antibody responses; enzymatic cleavage of immunoglobulins; and blocking complement activation. Most infectious
Consequences for pathogen transmission
Does tick-mediated host immunosuppression have an impact upon transmission and establishment of tick-borne disease-causing agents? The evidence being accumulated indicates that tick modulation of host immunity is an important factor in pathogen transmission. The most compelling work in this regard is that of Zeidener et al.[62]in which reconstitution of cytokines reduced by tick feeding provided protection against tick transmission of B. burgdorferi. Ramachandra and Wikel[60]reported that D.
Implications for control of tick-borne diseases
Tick-mediated host immunosuppression is an important factor in tick feeding and the transmission of tick-borne disease-causing agents. The observations regarding repeated infestation with pathogen-free ticks and the subsequent development of resistance to tick-transmitted infection is intriguing. Could a control strategy be developed that would target the factors in tick saliva that are essential for host immunosuppression and the transmission of infectious agents? Such a vector-blocking
Acknowledgements
The author's research described in this report resulted in part from support from The Centers for Disease Control and Prevention of the U.S. Public Health Service; the U.S. Department of Agriculture; the Oklahoma Center for Advancement of Science and Technology; and Oklahoma Agricultural Experiment Station Project OKL02174.
References (65)
Vector-borne parasitic diseases—an overview of recent changes
Int J Parasitol
(1998)Tick resistance: basophils in skin reactions of resistant guinea pigs
Int J Parasitol
(1973)- et al.
Cytokines and infectious diseases
Immunol Today
(1997) - et al.
IFN-γ, IL-2 and IL-4 mRNA expression in the skin and draining lymph nodes of BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks
Cell Immunol
(1994) - et al.
Subversion of the immune system by pathogens
Cell
(1994) - et al.
Tick–host immunology: significant advances and challenging opportunities
Parasitol Today
(1997) Ixodes dammini: salivary anti-complement activity
Exp Parasitol
(1987)- et al.
Ixodes dammini: salivary anaphylatoxin inactivating activity
Exp Parasitol
(1986) The physiology of itch
Parasitol Today
(1986)Boophilus microplus (Acari: Ixodidae): experimental infestations on cattle restrained from grooming
Exp Parasitol
(1969)
Ixodes scapularis: salivary kininase is a metallo dipeptidyl carboxypeptidase
Exp Parasitol
Biology of natural killer cells
Adv Immunol
Effects of cattle tick (Boophilus microplus) infestation on the bovine immune system
Vet Parasitol
Dermacentor andersoni: salivary gland proteins suppressing T-lymphocyte responses to concanavalin A in vitro
Exp Parasitol
Resurgent vector-borne diseases as a global health problem
Emerg Inf Dis
Bloodsucking ticks (Ixodidae)—vectors of disease of man and animals
Misc Publ Entomol Soc Am
Lyme borreliosis: relation of its causative agent to its vectors and hosts in North America and Europe
Ann Rev Entomol
Ecology of Ixodes dammini-borne human babesiosis and Lyme disease
Ann Rev Entomol
Emergence of the ehrlichioses as human health problems
Emerg Infect Dis
A new tick-borne encephalitis-like virus infecting New England deer ticks Ixodes dammini
Emerg Infect Dis
Ehrlichia chaffeensis, a new species associated with human ehrlichiosis
J Clin Microbiol
Ticks and Borrelia: model systems for investigating pathogen-arthropod interactions
Infect Agents Dis
Molecular characterization of a 6.6-kilodalton Borrelia burgdorferi outer membrane-associated lipoprotein (lp 6.6) which appears to be downregulated during mammalian infection
Infect Immun
Bloodstream-versus tick-associated variants of a relapsing fever bacterium
Science
Blood feeding arthropods: live syringes or invertebrate pharmacologists?
Infect Agents Dis
Host immunity to ticks
Ann Rev Entomol
Immunology of interactions between ticks and hosts
Med Vet Entomol
Cited by (212)
Molecular characterization of viruses found in honeybee (Apis mellifera) colonies infested with Varroa destructor and Nosema cerana in Egypt
2021, Molecular and Cellular ProbesCitation Excerpt :Our findings were consistent with previous studies that reported the globally distribution of DWV, acute bee paralysis complex viruses (i.e., ABPV, IAPV and KBV) as well as BQCV with the exception of Syria [31, 33, 34]. This is may be due to that the international movement of colonies for honey bee and bee product trade implies transportation of the bees and therefore the viruses they carry and also the ectoparasitic mite V. destructor, a biological or mechanical vector of honey bee viruses [35]. These results showed that there is a relationship between honey bee viruses, varroa mite and other pathogen, when one infects the honeybee this allow the others to infect and cause immune depression within the honeybee cell or hive.
Host immunomodulation by ascorbic acid ameliorates oxidative stress in caprine pediculosis—A pilot study
2019, Small Ruminant ResearchInnovations in dengue virus detection: An overview of conventional and electrochemical biosensor approaches
2024, Biotechnology and Applied Biochemistry