Sex difference in innate inflammatory response and macrophage polarization in Streptococcus agalactiae-induced pneumonia and potential role of microRNA-223-3p

• Published in: Scientific reports Vol. 12; no. 1; pp. 17126 - 14
• Main Authors: Deny, Maud, Arroba Nuñez, Luis Alexis, Romano, Marta, Denis, Olivier, Casimir, Georges, Chamekh, Mustapha
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/2499; 631/250/2504; 631/250/256; 631/337/384/331; Animals; Antagomirs - metabolism; Chemokines; Cytokines; Cytokines - metabolism; Female; Females; Gender differences; Humanities and Social Sciences; Inflammation - metabolism; Inflammatory diseases; Macrophages; Macrophages - metabolism; Male; Males; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Monocytes; multidisciplinary; Phenotypes; Pneumonia - metabolism; Polarization; Risk factors; Science; Science (multidisciplinary); Sex Characteristics; Sex differences; Streptococcus; Streptococcus agalactiae - genetics; Streptococcus infections
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-21587-5

While number of studies have shown that biological sex is a risk factor in the incidence and severity of infection-induced inflammatory diseases, the underlying mechanisms are still poorly understood. In this study, we compared the innate inflammatory response in male and female mice with group B streptococcal (GBS)-induced pneumoniae. Although male and female mice displayed similar bacterial burdens, males exhibited more innate inflammatory cytokines and chemokines and a higher proportion of infiltrating monocytes/macrophages. The analysis of the distribution of macrophage subtypes M1 (pro-inflammatory) versus M2 (anti-inflammatory) yielded a higher M1/M2 ratio in infected males compared with females. Given the importance of the chromosome X-linked microRNA-223-3p (miR-223-3p) in modulating the inflammatory process and macrophage polarization, we investigated its potential contribution in sex bias of GBS-induced innate inflammatory response. Knock-down of miR-223-3p with specific antagomiR resulted in increased inflammatory response and higher M1/M2 ratio following GBS infection. Notably, compared to male mice, we detected higher amount of miR-223-3p in macrophages from females that correlated negatively with M1 phenotype. These results suggest that differential expression of miR-233-3p may impact macrophage polarization, thereby contributing to fine-tune sex differences in inflammatory response.