Sand Fly Saliva EnhancesLeishmania amazonensisInfection by Modulating Interleukin-10 Production

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Abstract
After transmission through the bite of female sand flies,Leishmaniaspp. can cause a broad spectrum of disease manifestations collectively known as leishmaniases.L. amazonensisis endemic in South America, where it causes cutaneous, diffuse cutaneous, and visceral leishmaniasis. In this study, we have provided evidence that salivary gland extracts (SGE) ofLutzomyia longipalpisenhancesL. amazonensisinfection. BALB/c mice infected intradermally in the ear with 105metacyclic promastigotes ofL. amazonensistogether with SGE (equivalent to 0.5 gland) showed an early onset of disease and larger lesions that contained ∼3-log-units more parasites than did controls. To determine the potential mechanism underlying this enhancement, we assessed cytokine production via reverse transcriptase PCR and enzyme-linked immunosorbent assay. Mice coinjected with parasites and SGE displayed higher levels of interleukin-10 (IL-10) mRNA in the ear tissues, as well as higher levels of IL-10 in supernatants of restimulated draining lymph node (LN) cells, than did controls. Flow cytometric analysis revealed high frequencies of IL-10-producing CD4+and CD8+T cells in the draining LN of mice coinjected with the parasite and SGE. In addition, we examined bone marrow derived-macrophage cultures and detected increased IL-10 but decreased nitric oxide (NO) production in cells exposed to SGE prior to infection withL. amazonensis. Together, these results imply that the sand fly saliva facilitatesLeishmaniaevasion of the host immune system by modulating IL-10 production.