Alveolar Macrophages during Inflammation: A Balancing Act

Poor and Morales-Nebreda discuss the study by Llitjos and colleagues that used a double-infection experimental model to investigate the contribution of primary sepsis etiology to susceptibility to secondary bacterial pneumonia. Notably, they found that mice with cecal ligation and puncture (CLP)-induced polymicrobial peritonitis exhibit worsened mortality and decreased bacterial clearance from secondary Pseudomonas aeruginosa (PA) compared with animals initially challenged with Escherichia coli-induced pneumonia. Lung-specific immune cell subset analysis throughout the course of primary infection revealed a sequential and significant increase in Ly6Chi classical monocytes and AMs in the E. coli pneumonia group compared with the CLP-treated group, respectively. Measurement of the phagocytic and antigen-presenting capacity of AMs, combined with flow-cytometry analysis of activation and antiinflammatory markers and transcriptional profiling of AM following primary and secondary infection, led the authors to hypothesize that changes in AM numbers and function inform the divergent susceptibility to secondary lung PA infection.