Open AccessToll‐like receptor 2 has a prominent but nonessential role in innate immunity to Staphylococcus aureus pneumonia
Author(s) -
Skerrett Shawn J.,
Braff Marissa H.,
Liggitt H. Denny,
Rubens Craig E.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13491
Subject(s) - innate immune system , staphylococcus aureus , bronchoalveolar lavage , cathelicidin , immunology , microbiology and biotechnology , phagocytosis , bacterial pneumonia , immune system , pneumonia , inflammation , toll like receptor , biology , lung , antimicrobial peptides , medicine , antimicrobial , bacteria , antibiotics , genetics
Abstract Staphylococcus aureus is an important cause of acute bacterial pneumonia. Toll‐like receptor 2 ( TLR 2) recognizes multiple components of the bacterial cell wall and activates innate immune responses to gram‐positive bacteria. We hypothesized that TLR 2 would have an important role in pulmonary host defense against S. aureus . TLR null ( TLR 2 −/− ) mice and wild type ( WT ) C57 BL /6 controls were challenged with aerosolized S. aureus 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 TLR 2 −/− mice 4 and 24 h after infection in comparison with WT controls. Bronchoalveolar concentrations of cathelicidin‐related antimicrobial peptide also were reduced in TLR 2 −/− mice. Lung inflammation, measured by enumeration of bronchoalveolar neutrophils and scoring of histological sections, was significantly blunted in TLR 2 −/− 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 TLR 2 −/− mice. Bacterial clearance from the lungs was slightly impaired in TLR 2 −/− mice after low‐dose infection only; bacterial elimination from the lungs was slightly accelerated in the TLR 2 −/− mice after high‐dose infection. Survival after high‐dose intranasal challenge was 50–60% in both groups. TLR 2 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.