Distinct circulating neutrophil phenotypes are associated with S. pneumoniae versus E. coli murine models of pneumonia 3838

Abstract Description Rational. Despite potent antimicrobial therapies, pneumonia remains a significant global health threat. Our objective is to understand how different bacterial pneumonias affect neutrophil phenotype and function over time and identify regulators of neutrophil function and potential diagnostic tools. Methods. Lethal E. coli, or lethal or non-lethal serotypes of S. pneumoniae (SP3 vs SP19) was intratracheally instilled into the left lung lobe of 6–12-week-old or aged 90–100-week-old C57Bl/6 mice for 6, 24, or 48 hours. Neutrophils were isolated from blood and bronchioloalveolar lavage fluid (BALF), stained with a 24-color panel, and analyzed by flow cytometry (Cytek Aurora). Results and Conclusions. Neutrophil phenotype stratifies by tissue, time-point, and infection. Some discrete differences between neutrophils from young compared with aged mice were observed, including higher PD-L1 and lower CD16/32 expression. Notably, uninfected blood contains significantly higher proportion of CD101+, SPN-infected have a higher proportion of CD101Low and PD-L1+ or CXCR2High, and E. coli-infected have a higher proportion of CD101Low CXCR2Low SIRPαLow neutrophils. Blood tests to identify pathogens generally require bacteremia, and can require long overnight culturing times that would not be necessary for flow cytometry analysis of blood neutrophils. Our work suggests that blood neutrophil phenotype may have important diagnostic utility and should be investigated further. Funding Sources NIH grants K08 HL130582; R01 HL158732; T32 HL 007035. Topic Categories Mucosal and Regional Immunology (MUC)