Abstract
BackgroundThe saliva of sand flies strongly enhances the infectivity of Leishmania in mice. Additionally, pre-exposure to saliva can protect mice from disease progression probably through the induction of a cellular immune response.Methodology/Principal FindingsWe analysed the cellular immune response against the saliva of Phlebotomus papatasi in humans and defined the phenotypic characteristics and cytokine production pattern of specific lymphocytes by flow cytometry. Additionally, proliferation and IFN-γ production of activated cells were analysed in magnetically separated CD4+ and CD8+ T cells. A proliferative response of peripheral blood mononuclear cells against the saliva of Phlebotomus papatasi was demonstrated in nearly 30% of naturally exposed individuals. Salivary extracts did not induce any secretion of IFN-γ but triggered the production of IL-10 primarily by CD8+ lymphocytes. In magnetically separated lymphocytes, the saliva induced the proliferation of both CD4+ and CD8+ T cells which was further enhanced after IL-10 blockage. Interestingly, when activated CD4+ lymphocytes were separated from CD8+ cells, they produced high amounts of IFN-γ.ConclusionHerein, we demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of IL-10-producing CD8+ cells suggesting a possible detrimental effect of pre-exposure to saliva on human leishmaniasis outcome. However, the activation of Th1 lymphocytes by the saliva provides the rationale to better define the nature of the salivary antigens that could be used for vaccine development.
Highlights
Leishmaniasis includes a heterogeneous group of diseases that are caused by protozoan parasites of the genus Leishmania
Conclusion: we demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of IL-10-producing CD8+ cells suggesting a possible detrimental effect of pre-exposure to saliva on human leishmaniasis outcome
We analyzed the cellular immune response against the saliva of Phlebotomus papatasi developed in individuals naturally exposed to sand fly bites and demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of peripheral IL-10-producing
Summary
Pre-exposure to saliva completely abrogated the effects of the sand fly saliva and protected the host from disease progression [7,10,11]. This protective effect correlated with a strong delayed-type hypersensitivity (DTH) response and an early and increased in situ production of IFN-c and IL-12 [10]. Further experiments demonstrated that immunization with PpSP15 (gi|15963509) from P. papatasi saliva resulted in protection which was not ascribed to a humoral immune response [12] These data strongly supported the possibility that leishmaniasis could be prevented by vaccinating against sand fly saliva and suggest that the protective effect of the saliva might be associated with cell-mediated immunity. Pre-exposure to saliva can protect mice from disease progression probably through the induction of a cellular immune response
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