Toll‐like receptor 2 has a prominent but nonessential role in innate immunity to Staphylococcus aureus pneumonia. Issue 21 (15th November 2017)

• Record Type: Journal Article
• Authors: Skerrett, Shawn J.; Braff, Marissa H.; Liggitt, H. Denny; Rubens, Craig E.
• Is Part Of: Physiological reports. Volume 5:Issue 21(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-11-15
• Subjects: Alveolar macrophages -- bacterial pneumonia -- innate immunity -- Staphylococcus aureus -- toll‐like receptor 2; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13491
• Languages: English
• ISSNs: 2051-817X

Abstract

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 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 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. Abstract : Mice lacking Toll‐like receptor 2 exhibited significant reductions in the intrapulmonary production of pro‐inflammatory cytokines and chemokines, the recruitment of neutrophils to the lungs, the release of cathelicidin into the airspaces, and bacterial killing by alveolar macrophages after airway challenge with Staphylococcus aureus in comparison with wild‐type controls. However, bacterial clearance and survival after infection were not adversely affected by the absence of Toll‐like receptor 2.