Toll-like receptor 2 has a prominent but nonessential role in innate immunity to pneumonia.

is an important cause of acute bacterial pneumonia. Toll-like receptor 2 (TLR2) recognizes multiple components of the bacterial cell wall and activates innate immune responses to gram-positive bacteria. We hypothesized that TLR2 would have an important role in pulmonary host defense against TLR null (TLR2) mice and wild type (WT) C57BL/6 controls were challenged with aerosolized at a range of inocula for kinetic studies of cytokine and antimicrobial peptide expression, lung inflammation, bacterial killing by alveolar macrophages, and bacterial clearance. Survival was measured after intranasal infection. Pulmonary induction of most pro-inflammatory cytokines was significantly blunted in TLR2 mice 4 and 24 h after infection in comparison with WT controls. Bronchoalveolar concentrations of cathelicidin-related antimicrobial peptide also were reduced in TLR2 mice. Lung inflammation, measured by enumeration of bronchoalveolar neutrophils and scoring of histological sections, was significantly blunted in TLR2 mice. Phagocytosis of by alveolar macrophages in vivo after low-dose infection was unimpaired, but viability of ingested bacteria was significantly greater in TLR2 mice. Bacterial clearance from the lungs was slightly impaired in TLR2 mice after low-dose infection only; bacterial elimination from the lungs was slightly accelerated in the TLR2 mice after high-dose infection. Survival after high-dose intranasal challenge was 50-60% in both groups. TLR2 has a significant role in early innate immune responses to in the lungs but is not required for bacterial clearance and survival from pneumonia.