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Brossard, Michel

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Brossard, Michel
Affiliation principale
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https://libra.unine.ch/handle/123456789/308

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  • Publication
    Accès libre
    A family of putative metalloproteases in the salivary glands of the tick Ixodes ricinus
    (2008)
    Decrem, Yves
    ;
    Beaufays, Jérôme
    ;
    Blasioli, Virginie
    ;
    Brossard, Michel 
    ;
    Vanhamme, Luc
    ;
    Godfroid, Edmond
    Ticks are obligate blood-feeding arachnids. During their long-lasting blood meal, they have to counteract the protective barriers and defense mechanisms of their host. These include tissue integrity, pain, hemostasis, and the inflammatory and immune reactions. Here, we describe a multigene family coding for five putative salivary metalloproteases induced during the blood meal of Ixodes ricinus. The evolutionary divergence inside the family was driven by positive Darwinian selection. This came together with individual variation of expression, functional heterogeneity, and antigenic diversification. Inhibition of the expression of some of these genes by RNA interference prevented completion of the tick blood meal and affected the ability of the tick saliva to interfere with host fibrinolysis. This family of proteins could therefore participate in the inhibition of wound healing after the tick bite, thereby facilitating the completion of the blood meal.
  • Publication
    Accès libre
    Splenic dendritic cells pulsed with Ixodes ricinus tick saliva prime naive CD4+T to induce Th2 cell differentiation in vitro and in vivo
    (2007)
    Mejri, Naceur
    ;
    Brossard, Michel 
    Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in priming naive T cells. Using an in vitro priming system, we show that DCs incubated with Ixodes ricinus tick saliva initiate the Th2 differentiation of CD4+T cells. As determined with reverse transcription–PCR, the expression of IL-4 mRNA by these cells is higher than IFN-γ mRNA. Early endogenous production of IL-4 is thought to be important during the in vitro interaction of saliva-pulsed DCs with CD4+T cells. Its neutralization with specific mAbs inhibits the development of IL-4-secreting Th2 cells. Moreover, differentiated Th2 cells proliferate only when saliva-pulsed DCs and IL-1ß are added together early in the primary culture. As demonstrated by FACS analysis, the treatment in vitro of saliva-pulsed DCs by IL-1ß enhanced the expression of B7 and mainly CD40 co-stimulatory molecules, which provide sufficient signals to stimulate sensitized CD4+T cell proliferation. On the other hand, DCs treated with tick saliva only up-regulated mostly B7-2 co-stimulator expression and this was associated with differentiation of naive CD4+T cells into Th2 type of cells. The in vitro priming system is suitable to investigate the major elements implicated in the anti-tick immune response such as naive CD4+T cells, whole DCs population and tick saliva, and it can provide the possibility to delimit further the saliva molecules, the DC subsets and the type of host cells involved in the Th2 polarization. Corresponding in vivo experiments involving subcutaneous injection of tick saliva-pulsed DCs into BALB/c mice also elicited a Th2 immune response. Ex vivo cultures of draining lymph node T cells stimulated with tick saliva produced higher IL-4 : IFN-γ ratios compared with controls, confirming the relevance obtained in the in vitro priming model. These experiments demonstrate the importance of tick saliva in priming DCs to initiate a Th2-biased immune response in vitro and in vivo.
  • Publication
    Accès libre
    Identification of an Ixodes ricinus salivary gland fraction through its ability to stimulate CD4 T cells present in BALB/c mice lymph nodes draining the tick fixation site
    (1997)
    Ganapamo, F.
    ;
    Rutti, Bernard
    ;
    Brossard, Michel 
    BALB/c mice infested with larvae or nymphs of Ixodes ricinus develop in their lymph nodes a T cell-specific immune response triggered by salivary gland soluble antigens (SGA). SGA are apparently conserved in the 3 biological stages of I. ricinus ticks and are species specific. SGA derived from partially fed females I. ricinus stimulate lymph node T cells from mice infested with I. ricinus larvae or nymphs. In contrast, lymph node cells from mice infested with Amblyomma hebraeum nymphs do not respond. A chromatographic fraction enriched with a 65 kDa protein (IrSG65) isolated from salivary glands of I. ricinus partially fed females induces in vitro a specific T cell proliferation of lymph node cells from mice infested with I. ricinus nymphs. The depletion of CD4+ T cells drastically reduces the ability of lymphocytes from infested mice to proliferate after IrSG65 stimulation.