Tick Immune System: What Is Known, the Interconnections, the Gaps, and the Challenges.

Ticks are ectoparasitic arthropods that necessarily feed on the blood of their vertebrate hosts. The success of blood acquisition depends on the pharmacological properties of tick saliva, which is injected into the host during tick feeding. Saliva is also used as a vehicle by several types of pathogens to be transmitted to the host, making ticks versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding. In addition, some pathogens can colonize the ovaries of the tick and be transovarially transmitted to progeny. The tick immune system, as well as the immune system of other invertebrates, is more rudimentary than the immune system of vertebrates, presenting only innate immune responses. Although simpler, the large number of tick species evidences the efficiency of their immune system. The factors of their immune system act in each tick organ that interacts with pathogens; therefore, these factors are potential targets for the development of new strategies for the control of ticks and tick-borne diseases. The objective of this review is to present the prevailing knowledge on the tick immune system and to discuss the challenges of studying tick immunity, especially regarding the gaps and interconnections. To this end, we use a comparative approach of the tick immune system with the immune system of other invertebrates, focusing on various components of humoral and cellular immunity, such as signaling pathways, antimicrobial peptides, redox metabolism, complement-like molecules and regulated cell death. In addition, the role of tick microbiota in vector competence is also discussed.

Serologic evidence of rickettsial diseases associated with tick bites in workers of urban veterinary clinics.

BACKGROUND & OBJECTIVES: Rickettsial and other zoonotic diseases are a latent risk for workers of veterinary clinics. The objective of this study was to evaluate the prevalence and the associated risk factors of parasitosis caused by Rhipicephalus sanguineus, and to estimate the seroprevalence of rickettsial diseases in workers of urban veterinary clinics of Juárez city, México. METHODS: The participants of the study were recruited from 63 private veterinary clinics and hospitals. The serological analysis of the blood samples collected was carried out using immunofluorescence assay (IFA). The statistical analysis for prevalences, risk factors, and correlation was performed with the SAS program. RESULTS: In total, 167 veterinary workers were included in the study. The prevalence of tick bites was 40% (67/167), and the risk factors associated with the occurrence of bites included the activities performed in the clinic and the number of labour hours spent per week. About 21% (35/167) of participants were seropositive to R. rickettsii, 28% (47/167) to Ehrlichia chaffeensis, and 24% (40/167) to Anaplasma phagocytophilum. A correlation was observed between: the number of workers in the clinics and the proportion of tick bites (r2 = 0.865); the prevalence of bites and the seropositivity of the participants to at least one pathogen (r2 = 0.924); and the number of bites per individual and infection to pathogens (r2 = 0.838). INTERPRETATION & CONCLUSION: Workers in urban veterinary clinics are highly exposed to tick bites and, therefore, to the diseases they transmit. Hence, it is important to implement prevention measures and perform constant monitoring of these diseases.

Molecular characterization of the recombinant protein RmLTI-BmCG-LTB: Protective immunity against Rhipicephalus (Boophilus) microplus.

The bovine tick Rhipicephalus (Boophilus) microplus is found in several tropical and subtropical regions of the world. This parasite transmits pathogens that cause disease, such as babesiosis (Babesia bovis and B. bigemina) and anaplasmosis (Anaplasma marginale). Tick infestations cause enormous livestock losses, and controlling tick infestations and the transmission of tick-borne diseases remains a challenge for the livestock industry. Because the currently available commercial vaccines offer only partial protection against R. (B.) microplus, there is a need for more efficient vaccines. Several recombinant antigens have been evaluated using different immunization strategies, and they show great promise. This work describes the construction and immunological characterization of a multi-antigen chimera composed of two R. (B.) microplus antigens (RmLTI and BmCG) and one Escherichia coli antigen (B subunit, LTB). The immunogenic regions of each antigen were selected and combined to encode a single polypeptide. The gene was cloned and expressed in E. coli. For all of the experiments, two groups (treated and control) of four Angus heifers (3-6 months old) were used. The inoculation was performed via intramuscular injection with 200 µg of purified recombinant chimeric protein and adjuvated. The chimeric protein was recognized by specific antibodies against each subunit and by sera from cattle inoculated with the chimera. Immunization of RmLTI-BmCG-LTB cattle reduced the number of adult female ticks by 6.29% and vaccination of cattle with the chimeric antigen provided 55.6% efficacy against R. (B.) microplus infestation. The results of this study indicate that the novel chimeric protein is a potential candidate for the future development of a more effective vaccine against R. (B.) microplus.

Tick-borne diseases and autoimmunity: A comprehensive review.

Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.

Serological evidence of Rickettsia and Coxiella burnetii in humans of Buenos Aires, Argentina.

In Buenos Aires city (Argentina), the circulation of these agents has been detected mainly in vectors and animals, few human cases having been described. The aim of our study was to determine the seroprevalence of Rickettsia (spotted fever--SFG--and typhus--TG--groups) and Coxiella burnetii (Q fever agent) in residents of Buenos Aires city. The study involved 99 participants. Rickettsia IgG antibodies against SFG and TG were detected by IFA in 28.3% and 16.2% of serum samples, respectively. SFG titers were mostly 1/64 (53.6%) with a maximum of 1/512 (3.5%) whereas TG titers ranged between 1/64 (62.5%) and 1/256 (6.3%). Only one sample showed a titer of 1/32 for C. burnetii (phases I and II). The circulation of these pathogens in urban areas such as the city of Buenos Aires should be considered by health services, especially at the primary care level.

Immune response to Babesia bigemina infection in pregnant cows.

Babesiosis is a tick-borne disease of cattle caused by Babesia bigemina and Babesia bovis and is transmitted by the tick vector Boophilus microplus. In this study, we investigate B. bigemina infection regarding the clinical infection, T cell distribution, and cytokine profile during the acute phase of an experimental infection in pregnant cows.

The safety and efficacy of Australian tick-borne disease vaccine strains in cattle in Paraguay.

Glycerol preserved, frozen tick-borne disease vaccine strains developed in Australia were imported into Paraguay to test their safety in pregnant Holando heifers and their efficacy against challenge from inoculated local field strains of Babesia bigemina, B. bovis and Anaplasma marginale in Hereford X Criolla heifers. The two Babesia strains proved to be safe and the B. bovis K strain was very effective in providing immunity to a local field strain of B. bovis. The B. bigemina efficacy trial was inconclusive, possibly due to the avirulent nature of the local field strain used in challenge. The A. centrale strain did not prove to be as safe as would be desirable in safety trials, neither did it provide as good protection as the Babesia strains in the efficacy trial. It was concluded that the Babesia strains provided good protection against field challenge in Paraguay and were safe to use in highly susceptible cattle, however an alternative to A. centrale should be sought to provide protection against local strains of A. marginale.

Validation and comparison of three enzyme-linked immunosorbent assays for the detection of antibodies to Cowdria ruminantium infection.

Serological tests for Cowdria ruminantium infection have been hampered by low specificity. Here, an indirect ELISA based on purified antigen, a competitive ELISA using a recombinant major antigenic protein (MAP-1) and an indirect ELISA based on the MAP-1B region of the recombinant MAP-1 were compared. The tests were validated using 3000 sera of ruminants from 14 islands of the Lesser Antilles as well as sequential serum samples from 10 cattle, 17 goats and 10 sheep vaccinated with inactivated C. ruminantium in ISA 50 adjuvant and from 14 goats infected with a virulent culture supernatant. All tests detected significantly higher percentages of positives on Antigua, Guadeloupe and Marie-Galante, where C. ruminantium had been isolated before. Overall specificity calculated with sera from the other 11 heartwater-free islands was 98.1%, 98.5%, and 99.4% for the ELISA based on crude antigen, recombinant MAP-1 and MAP-1B, respectively. Sensitivities observed with sequential serum samples were similar for all tests. Tests based on recombinant antigens, especially the MAP-1B, showed improved specificity, suggesting their use for epidemiological studies in regions where the distribution of cowdriosis is unknown. In addition, the competitive ELISA is useful for studies in wildlife for which species-specific conjugates do not exist.

Cross-sectional estimation of Babesia bovis antibody prevalence in an area of Argentina used for extensive cattle breeding as an aid to control babesiosis.

The prevalence of Babesia bovis antibodies was estimated by using an ELISA (98% sensitivity and 95% specificity). Sera were obtained from 165 calves (mean age and standard deviation: 9.7 +/- 2.7 months) from an area in Argentina known to be unfavourable for the development of the vector tick, Boophilus microplus. The area comprised about 300,000 ha used for cattle breeding. The cattle population of 55,000 included 12,000 cattle under 1 year of age. Cattle were maintained mainly on natural grasses in communal lands. The true prevalence of antibodies to Babesia bovis was 12.2% with a confidence interval of 7.6% to 18.2%, and an inoculation rate (h; daily probability of infection) of 0.0004. This confidence interval has its lower boundary in the area of endemic stability due to low h of Babesia bovis by the vector tick and the upper limit in the area of endemic instability. This type of analysis could help to decide the implementation of preventive measures (e.g. vaccination) rationally, even in remote areas (such as the one of the present study) with an extensive cattle industry.