Host Defense Mechanisms Triggered by Microbial Lipoproteins Through Toll-Like Receptors

TLDR

IL‑12 is essential for cell‑mediated immunity, yet the microbial molecules that trigger its production by macrophages and the underlying mechanisms remain largely unknown. Microbial lipoproteins activate Toll‑like receptors on human macrophages, inducing IL‑12 and nitric‑oxide production via iNOS, thereby initiating innate defense pathways against pathogens.

Abstract

The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.