Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages

TLDR

Recognition of mycobacterial cell‑wall components triggers macrophage secretion of TNF‑α and other cytokines essential for protective inflammation. The study demonstrates that TLR2 is indispensable for TNF‑α production in macrophages in response to M.

Abstract

The recognition of mycobacterial cell wall components causes macrophages to secrete tumor necrosis factor alpha (TNF-alpha) and other cytokines that are essential for the development of a protective inflammatory response. We show that toll-like receptors are required for the induction of TNF-alpha in macrophages by Mycobacterium tuberculosis. Expression of a dominant negative form of MyD88 (a signaling component required for toll-like receptor signaling) in a mouse macrophage cell line blocks TNF-alpha production induced by M. tuberculosis. We identify toll-like receptor-2 (TLR2) as the specific toll-like receptor required for this induction by showing that expression of an inhibitory TLR2 (TLR2-P681H) blocks TNF-alpha production induced by whole M. tuberculosis. Further, we show that TLR2-dependent signaling mediates responses to mycobacterial cell wall fractions enriched for lipoarrabinomannan, mycolylarabinogalactan-peptidoglycan complex, or M. tuberculosis total lipids. Thus, although many mycobacterial cell wall fractions are identified to be inflammatory, all require TLR2 for induction of TNF-alpha in macrophages. These data suggest that TLR2 is essential for the induction of a protective immune response to mycobacteria.