Modulation of Host-Immune Responses by Ticks (Acari: Ixodidae): Effect of Salivary Gland Extracts on Host Macrophages and Lymphocyte Cytokine Production

Abstract

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.

Characterization of a Novel Salivary Immunosuppressive Protein from Ixodes ricinus Ticks

“…Indeed, SGE, prepared daily from engorging Dermacentor andersoni, suppressed IL-1 secretion by macrophages only from day 0 to day 5 of engorgement, whereas TNF-␣ production was suppressed during the entire blood meal by these cells (18). Except for the fact that IL-1 expression is not inhibited, the modulating effect of Iris on T cell and macrophage responsiveness seems to mimic the SGE properties, suggesting that Iris is an important salivary factor in the modulation of the local host immune response.…”

“…Tick salivary gland extracts (SGE) modulates host immune response by modifying both lymphocyte and monocyte activities. For example, T lymphocyte proliferation in response to mitogens (17) and the production of Th1 cytokines as IFN-␥ and IL-2 are inhibited by SGE (18). Moreover, Th2 type cytokine production such as IL-10, IL-5, and IL-4 is in general slightly enhanced (4,5).…”

Prostaglandin E2 Is a Major Inhibitor of Dendritic Cell Maturation and Function in Ixodes scapularis Saliva

“…Furthermore, in vivo and in vitro inhibition of cytokines has been demonstrated by Ixodes scapularis and other species of hard ticks. For example, macrophage production of IL-1 and TNF-␣, as well as lymphocyte production of IL-2 and IFN-␥, were diminished in the presence of Dermacentor andersoni salivary gland extracts (16). In addition, splenocytes from C3H/ HeJ mice infested with I. scapularis nymphs presented decreased production of IL-2 and IFN-␥ and increased production of IL-4 and IL-10 when stimulated with Con A (17,18).…”

The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae)

“…Immunomodulators affecting NK cell function (Kopecky and Kuthejlova, 1998)-in addition to inhibitors of the proliferation of T lymphocytes and an IL-2 binding activity-also are present in this secretion (Ramachandra and Wikel 1992;Gillespie et al, 2001). Finally, saliva is important in transmission of tick-borne pathogens, as it may enhance pathogen transmission (for a review, see Wikel, 1999).…”