The role of CD11b in Streptococcus pneumoniae induced lung inflammation

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 CD11bKO 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 (AECs) in CD11bKO mice compared to wt mice. Furthermore, wt alveolar macrophages (AMs) significantly upregulated CD11b upon S.p. infection, suggesting an important function of CD11b in inflammatory AM phenotype. Indeed, CD11bKO AMs showed higher MPO expression and respiratory burst compared to the wt counterparts. AMs isolated from CD11bKO mice and challenged with S.p. in vitro produced higher levels of pro-inflammatory cytokines and chemokines such as IL-6 and CXCL1 than wt AMs. Our results suggest that CD11b protects against tissue damage by limiting AM activation and neutrophil recruitment.