Ixodes ricinus tick salivary gland extract inhibits IL‐10 secretion and CD69 expression by mitogen‐stimulated murine splenocytes and induces hyporesponsiveness in B lymphocytes

Abstract

Tick saliva contains immunosuppressive factors allowing this blood-feeding ectoparasite to remain on hosts and enhancing pathogen transmission. In this study, we examined the modulation of mitogen-induced activation of naive murine splenocytes by the saliva and salivary gland extract (SGE) of I. ricinus ticks. We found that saliva-specific factors reduced IL-10 production by both concanavalin A (ConA) and lipopolysaccharide (LPS) stimulated splenocytes. The LPS-induced IL-10 production is 10 times more sensitive to SGE than the ConA-induced IL-10 production. Flow cytometric analysis determined that SGE particularly inhibited B (B220+) cell IL-10 production in mitogen-stimulated splenocyte preparations. Moreover, SGE reduced the early activation marker CD69 expression on ConA-activated T cells and also on B cells in presence of ConA or LPS. Annexin V and Via-probe staining demonstrated that SGE did not increase cell death in activated splenocytes and slightly decreased apoptosis in B lymphocytes. By employing assays with isolated B cells, we further showed that SGE had a direct effect on B cells and inhibited LPS-induced B cell proliferation. Taken together, our results indicate that salivary immunomodulators induce hyporesponsiveness to mitogen in both T and B cells, and that a direct B-cell inhibitory activity is present in tick saliva.

Toward an Understanding of the Molecular Mechanism for Successful Blood Feeding by Coupling Proteomics Analysis with Pharmacological Testing of Horsefly Salivary Glands

“…IL-10 is a cytokine suppressor of T-cell proliferative and cytokine responses. IL-10 can inhibit the elaboration of proinflammatory cytokines, for example IFN-␥ (16,17,31). Tabimmunregulins possibly up-regulated the IL-10 production to inhibit IFN-␥ secretion in the current experiments.…”

Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

“…One microgram of total RNA was reverse transcribed using oligo(dT) [12][13][14][15][16][17][18] and Superscript II reverse transcriptase (GIBCO-Invitrogen). Quantitative real-time PCR was performed in a Bio-Rad (Hercules, CA) iCycler with Bio-Rad iQ SYBR green Supermix.…”

“…Especially for ticks, which are characterized by their extended feeding time, a broad repertoire of immune modulatory activities has been described. These modulatory activities include the predominant induction of a Th2 response with an overall inhibition of proinflammatory and Th1 cytokines (23,24,38,54), suppression of the effector functions of antigen-presenting cells (APCs) (5,26,28,59), and modulation of T-cell (28,59) and B-cell (17,18) responses, as well as the inhibition of granulocyte infiltration (39,53) and NK-mediated cytotoxicity (25). Illustrating the importance of salivary components for pathogen transmission, the tick protein Salp15 was shown to significantly increase the infectivity of Borrelia burgdorferi spirochetes in mice (50).…”

Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

“…Tick saliva and/or tick salivary gland extract (SGE) 3 have been shown to inhibit several functions of the immune system, including activation of the alternative complement pathway (3), phagocytosis of pathogens and production of inflammatory cytokines by macrophages (4 -6), NK cell activity (7), as well as T cell (5,8,9) and B cell proliferation (10). Moreover, tick saliva has been reported to favor development of a Th2-type immune response, characterized by production of high levels of IL-4 and IL-10 and low levels of IFN-␥ and IL-12 (11)(12)(13)(14).…”