Ixodid tick infestation induces host acquired resistance, which involves immunoglobulin cell-mediated and complement-dependent effector pathways. Ticks have developed countermeasures to modulate host antiarthropod responses. Ixodid-mediated host immunomodulation results in vitro in reduced responsiveness to T-lymphocyte mitogens for cells obtained from infested hosts and impaired antibody responses to a thymic dependent antigen. Salivary gland extracts from days 0-9 of engorgement from unmated, female Dermacentor andersoni Stiles suppressed lymphocyte proliferative responses (LPS) to the T-cell mitogen Con A up to 68.4%, whereas responsiveness to E. coli LPS was enhanced. Cytokines assessed in this study included interleukin-1, IL-1, and tumor necrosis factor (TNF) alpha produced by macrophages, and interleukin-2, IL-2, and gamma interferon (IFN-G) secreted by T-lymphocytes. Salivary gland extracts prepared from tissues obtained on days 0-5 of engorgement suppressed IL-1 elaboration from 89.8% on day 0 through 37.5% on day 6. Levels of TNF were reduced from 40.7 to 94.6% throughout the course of the study. Production of IL-2 was suppressed by 14.1-31.9%, and IFN-G was reduced by 8.7-57.0%. Reduced IL-1 levels during the early phases of feeding indicated reduced host ability to activate T-lymphocytes and provide costimulatory, differentiation, and development signals for B-cells. Both IL-1 and TNF are endogenous pyrogens and activate polymorphonuclear leukocytes. Activities of TNF and IFN-G include antiviral properties and induction of expression of class I and II major histocompatibility complex molecules, which are critical components in the recognition of antigen by T-lymphocytes. The autocrine role of IL-2 in proliferation of T-lymphocytes is central to the development of immune reactivity involving T-cell regulation or effector functions or both. Reductions in cytokine levels would suppress immune responses directed toward immunogens introduced into the host during the course of tick feeding. These results indicates that immunomodulation of the host during tick feeding facilitates engorgement and pathogen transmission.

Female BALB/c mice were infested four times with pathogen-free Ixodes scapularis nymphs prior to infestation with nymphs infected with Borrelia burgdorferi B31. Each infestation was separated by a 14-day tick-free period. Mean weights of fed ticks and percentage reaching repletion did not indicate development of acquired resistance. Only 16.7% of mice repeatedly infested with pathogen-free ticks prior to infected I. scapularis nymph challenge became positive for B. burgdorferi. One hundred percent of control mice infested only with infected ticks were culture positive for B. burgdorferi.

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Cattle and laboratory animal species-acquired resistance to tick infestation has an immunological basis involving antigen presenting cells, B-lymphocytes, T-lymphocytes, and cytokines. Tick infestation has been shown to impair guinea pig antibody responses to a thymic-dependent antigen and in vitro responsiveness of lymphocytes to T-cell mitogens. Tick salivary gland extracts inhibited in vitro proliferative responses of normal murine lymphocytes to the T-cell mitogen concanavalin A (Con A) and enhanced reactivity of normal B-lymphocytes to the mitogen E. coli lipopolysaccharide (LPS). Salivary gland extracts collected daily during engorgement were shown to inhibit normal murine macrophage elaboration of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF) as well as murine T-lymphocyte production of interleukin-2 (IL-2) and interferon-gamma (IFN-G). Peripheral blood mononuclear cells collected from purebred Bos indicus and B. taurus were significantly inhibited in their in vitro responses to Con A by salivary gland extracts prepared daily from female Dermacentor andersoni stiles during the course of engorgement. Percentage of suppression of Con A responsiveness was similar for both B. indicus and B. taurus cells. The overall responsiveness of B. indicus derived T cells is significantly greater than that of similar cells from B. taurus, when mean counts per minute of methyl-tritiated-thymidine incorporation were compared for both groups. Cells of B. indicus origin were 34.5% more reactive. In vitro responsiveness of the same cell populations to LPS were significantly enhanced by the presence of tick salivary gland extracts. B. indicus lymphocyte reactivity to LPS was significantly greater (42.9%) than that of similar B. taurus cells in the absence of salivary gland extracts. B. indicus and B. taurus macrophage elaboration of IL-1 were suppressed in a similar manner by tick salivary gland extracts prepared on days 5-9 of engorgement. B. indicus macrophages produced more IL-1 than similar cells of B. taurus origin either in the presence (45.6%) or absence (43.0%) of LPS. Macrophages derived from both genetic backgrounds were significantly suppressed in their LPS induced production of TNF in the presence of tick salivary gland extracts collected on days 0-9 of engorgement. B. indicus might be able to develop more vigorous immune responses to foreign immunogens presented to the animal during tick feeding.

A 36-kDa soluble protein was found in the salivary glands of female Dermacentor andersoni (Stiles) ticks that suppressed the in vitro proliferative response of murine splenocytes to concanavalin A (Con A). Incubating the purified protein with splenocytes reduced the incorporation of thymidine into the DNA of proliferating T-lymphocytes by more than 90% compared with cells exposed to Con A and buffer alone. The N-terminal amino acid sequence of the immunosuppressant protein was determined to be NH2-Leu-His-Lys-Ala(Asp)-Lys-Ile-Val-Lys-Leu-Thr -Glu-Glu-Ala -Arg-Lys-Tyr-Val-Gly-Arg-Xxx-Xxx-Thr-Thr-Ala-Leu-Gly-. Although the sequence exhibited a modest degree of similarity with a segment of immunoglobulin-binding protein found in several species of mammals, the mode of action of the immunosuppressant protein is unknown. This protein may play an important role in suppressing the host's acquisition of resistance to ticks.