CD11b Protects Against Tissue Damage During S. pneumoniae Lung Infection by Limiting Neutrophil Recruitment

CD11b is an integrin of the β2 family important for leukocyte adhesion, immunological synapse formation, as well as regulation of signalling from heterologous receptors. Here, we have investigated the role of CD11b in Streptococcus pneumoniae (S. p.) lung infection. We have found that CD11b−/− mice exhibit exacerbated inflammation to S. p. marked by worsened histopathology score, higher levels of pro-inflammatory cytokines and chemokines and increased neutrophil recruitment into the alveolar space. Lung light sheet microscopy revealed increased destruction of alveolar epithelial cells in CD11b−/− mice compared to wt mice. Furthermore, wt alveolar macrophages (AMs) significantly upregulate CD11b upon S. p. infection, suggesting an important function of CD11b in inflammatory AM phenotype. Indeed, CD11b−/− AMs have higher MPO expression and respiratory burst compared to the wt counterparts. AMs isolated from CD11b−/− mice and challenged with S. p. in vitro produce higher levels of pro-inflammatory cytokines and chemokines such as IL-6 and CXCL1 than wt AMs. Our results demonstrate that CD11b protects against tissue damage by limiting AM activation and neutrophil recruitment.