Immunosuppression and cytokine production in mice infested with Ixodes ricinus ticks: a possible role of laminin and interleukin‐10 on the in vitro responsiveness of lymphocytes to mitogens

Abstract

SUMMARYT cells from BALB/c mice infested 9 days before with Ixodes ricinus nymphs had a suppressed response to in vitro concanavalin A (Con A) stimulation compared to cells from uninfested mice. When laminin (the main component of the extracellular matrix) was used as a coating agent, the Con A response of naive mice was characterized by a decrease in cell proliferation, whereas there was no significant effect on the mitogen response of cells from infested mice. In contrast, an increased response to lipopolysaccharide (LPS) was observed when assaying lymph node cells of infested mice, probably reflecting an increase in B-lymphocyte number or activity. LPS cell stimulation was not modified by laminin. Supernatants of lymph node cells, taken 9 days after the first infestation of mice, stimulated with Con A in vitro, contained interleukin-10 (IL-10) but no significant levels of IL-5 as tested by enzyme-linked immunosorbent assay. At this stage of the infestation all T cells reactive with tick antigens generated in lymph nodes that drain the tick fixation site, were CD4 cells, as determined by CD4 depletion. With cells taken 9 days after the third infestation an increase of IL-5 and IL-10 was observed. The IL-10 levels were higher than the IL-5. According to these observations, we conclude that the reduction of T-cell proliferation in response to Con A observed in lymph node cells from infested mice, may be due to the combined effect of laminin interaction with T lymphocytes during migration and IL-10 production by these lymphocytes.

Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding.

“…[12][13][14] Indeed, the alternative pathway of the complement is inhibited 15,16 and the activity of lymphoid cells is modified. [17][18][19][20][21][22][23] For tick infestation, interleukin (IL)-4, IL-5, and IL-10 induction and IL-2 and interferon gamma inhibition [24][25][26] are observed, indicating a polarized Th2 host immune response. 13 It has also been observed that during the bloodmeal, new mRNAs are induced in the salivary glands, leading to the synthesis of a wide range of new proteins.…”

Characterization of a Novel Salivary Immunosuppressive Protein from Ixodes ricinus Ticks

“…Resistance to tick infestation implicates both innate and acquired immunity and is characterized by reduced feeding, molting, and mating capabilities that may lead to the death of the parasite. Acquired immunity of resistant hosts is mediated by a polarized Th1-type immune response, involving IFN-␥ 1 production and delayed type hypersensitivity reaction (3,4).…”

“…Some hosts are unable to counteract the tick infestation (4). Indeed, during their blood meal, ticks circumvent host defenses via pharmacologically active components secreted in their saliva.…”

“…These factors of major importance for tick survival can modulate innate and acquired immunity. In this way, the leukocyte responsiveness is modified during tick feeding (5). For example, cytokine production is modulated, inducing a polarized Th2 immune response (4,6).…”

“…In this way, the leukocyte responsiveness is modified during tick feeding (5). For example, cytokine production is modulated, inducing a polarized Th2 immune response (4,6). Therefore, the complex tickhost molecular interactions can be considered as a competition between host defenses raised against the parasite and the tick evasion strategies, facilitating feeding for an extended period.…”