Neutrophil Inhibitory Receptors Expression Is Distinct During Gram-Positive and -Negative Pneumonia and Affects Neutrophil Function
نویسندگان
چکیده
Abstract Rational: Despite effective antimicrobial therapy, morbidity and mortality from pneumonia remains high. Honing our understanding of immune dysfunction in is now crucial for developing targeted therapeutics. Our objective to understand how different lethal bacterial pneumonias affect neutrophil phenotype function over time identify regulators function. Methods: Mice were intratracheally instilled with E. colior S. pneumoniae(SP3) 6, 24 or 48h neutrophils isolated either bronchioloalveolar lavage fluid (BALF) peripheral blood. Neutrophil surface marker expression (SME) was analyzed via 25-color panel run on a Cytek Aurora spectral flow cytometer (SFC). Data FlowJo gated live, single cell, CD45+Ly6G+ neutrophils, opt-SNE data visualization, Phenograph unbiased clustering. For clearance assays, bone marrow Percoll, then incubated blocking antibodies against inhibitor receptors (IRs) (PD-L1, SIRPα, VISTA, CD200R), soluble ligands, media only. Neutrophils cocultured SP3 coli. Media bacteria-neutrophil cultures plated agar the colonies counted. Results Conclusions: Using SFC, we identified pathogen- timepoint-specific differences SME IRs PD-L1, VISTA CD200R. Modulating IR signaling by stimulating them impacts neutrophils’ ability clear bacteria. In sum, suggests that modulates their response adapt specific pathogens. may play role regulating these dynamic responses, making potential therapeutic target. NIH grants K08 HL130582 (KET) R01 HL158732 (KET).
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.71.19