Differential Roles of Toll-Like Receptors 2 and 4 in In Vitro Responses of Macrophages toLegionella pneumophila

Abstract

The role of Toll-like receptors (TLRs) in innate immunity toLegionella pneumophila, a gram-negative facultative intracellular bacterium, was studied by using bone marrow-derived macrophages and dendritic cells from TLR2-deficient (TLR2−/−), TLR4−/−, and wild-type (WT) littermate (C57BL/6 × 129Sv) mice. Intracellular growth ofL. pneumophilawas enhanced within TLR2−/−macrophages compared to WT and TLR4−/−macrophages. There was no difference in the bacterial growth within dendritic cells from WT and TLR-deficient mice. Production of interleukin-12p40 (IL-12p40) and IL-10 after infection withL. pneumophilawas attenuated in TLR2−/−macrophages compared to WT and TLR4−/−macrophages. Induction of IL-12p40, IL-10, and tumor necrosis factor alpha secretion from macrophages by theL. pneumophila dotOmutant, which cannot multiply within macrophages, and heat-killed bacteria, was similar to that caused by a viable virulent strain. There was no difference between the WT and its mutants in susceptibility to the cytopathic effect of bacteria. AnL. pneumophilasonicated lysate induced IL-12p40 production by macrophages, but that of TLR2−/−macrophages was significantly lower than those of WT and TLR4−/−macrophages. Treatment ofL. pneumophilasonicated lysate with proteinase K and heating did not abolish TLR2-dependent IL-12p40 production. Our results show that TLR2, but not TLR4, is involved in murine innate immunity againstL. pneumophila, although other TLRs may also contribute to innate immunity against this organism.

Part of Endotoxins research · Curated by Lauren Lowenstein, The Biotoxin Lady