Platelet activating factor receptor-deficient mice present delayed interferon-γ upregulation and high susceptibility to Leishmania amazonensis infection

Abstract: We investigated the role of the platelet activation factor (PAF) receptor (PAFR) in the outcome of infection with Leishmania amazonensis. PAFR deficient (PAFR−/−) mice were infected with L. amazonensis and the course of infection was followed. We found that PAFR−/− mice in the C57BL/6 background were more susceptible to infection with L. amazonensis than the wild-type controls, as seen both by lesion size and parasite number at the site of infection. Interferon (IFN)-γ production was delayed in PAFR−/− mice, and lower levels of Ccl5 were found in lesions. Expression of nitric oxide synthase-2 mRNA was found impaired in PAFR−/− associated with higher levels of arginase-1 mRNA. Moreover, higher levels of antibodies were produced in response to L. amazonensis by PAFR−/− mice. We conclude that signaling through the PAFR is essential for the ability of the murine host to control L. amazonensis infection by driving an adequate immune response. [Copyright &y& Elsevier]