Phagocytosis of Leishmania mexicana amastigotes by macrophages leads to a sustained suppression of IL-12 production

Abstract

Healing of leishmaniases is dependent on activation of parasitized macrophages (MΦ) by IFN-γ, which is secreted by Leishmania-specific Th1 cells. IL-12 enhances IFN-γ production by Th1 cells and is crucial for cure. The host cells of Leishmania sp., MΦ, are a main source of IL-12 in vivo. We report that infection of quiescent murine MΦ with L. mexicana or L. major amastigotes does not induce IL-12 production. Moreover, infection suppresses IL-12 secretion by MΦ activated by LPS, by CD40 cross-linking or cognate interaction with Th1 cells. IL-12 secretion is also suppressed in MΦ activated after phagocytosis of latex beads. Suppression is independent of engagement of CR3 or FcγR during phagocytosis, is not mediated by IL-10 and does not alter steady state IL-12p40 mRNA levels. In addition, suppression of IL-12 secretion does not depend on MΦ activation concurrent to infection. In contrast, NO production was not inhibited. Thus, MΦ effector functions are differentially affected and this may be a general effect of phagocytosis of non-activating particles. The possible implications of this effect on the infection are discussed.