Non–Mannose-capped Lipoarabinomannan Induces Lung Inflammation via Toll-like Receptor 2

Non-mannose-capped lipoarabinomannan (AraLAM) is part of the cell membrane of atypical mycobacteria. To determine the capacity of AraLAM to induce lung inflammation in vivo and to determine the signaling receptors involved herein, wild-type (WT) mice, lipopolysaccharide binding protein knockout mice, CD14-deficient (CD14 KO) mice, Toll-like receptor (TLR) 4 mutant mice, or TLR2 KO mice were intranasally inoculated with purified AraLAM. AraLAM induced high lung levels of tumor necrosis factor, interleukin-1beta, interleukin-6, and cytokine-induced neutrophil chemoattractant (KC) and an influx of neutrophils into the pulmonary compartment of WT mice. Lipopolysaccharide binding protein knockout, CD14 KO, and TLR4 mutant mice displayed similar inflammatory responses as WT mice, whereas in TLR2 KO mice, AraLAM-induced lung inflammation was strongly diminished. In addition, TLR2 KO mice, but not CD14 KO or TLR4 mutant mice, displayed a delayed clearance of pulmonary infection with the atypical AraLAM expressing Mycobacterium smegmatis. These data indicate that TLR2 is the signaling receptor for purified AraLAM in the lung in vivo and that this receptor contributes to an effective clearance of M. smegmatis from the pulmonary compartment.