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

Abstract

Staphylococcus aureus 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 S. aureus. TLR null (TLR2/ ) mice and wild type (WT) C57BL/6 controls were challenged with aerosolized S. aureus at a range of inoc-ula for kinetic studies of cytokine and antimicrobial peptide expression, lung inflammation, bacterial killing by alveolar macrophages, and bacterial clear-ance. 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 bron-choalveolar neutrophils and scoring of histological sections, was significantly blunted in TLR2/ mice. Phagocytosis of S. aureus 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 S. aureus in the lungs but is not required for bacterial clearance and survival from S. aureus pneumonia.