Progressive Control of Streptococcus agalactiae-Induced Innate Inflammatory Response Is Associated with Time Course Expression of MicroRNA-223 by Neutrophils

• Published in: Infection and immunity Vol. 88; no. 12
• Main Authors: Deny, Maud, Romano, Marta, Denis, Olivier, Casimir, Georges, Chamekh, Mustapha
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 16.11.2020
• Subjects: Animals; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Chemokine CXCL2 - genetics; Chemokine CXCL2 - metabolism; Chemokines - metabolism; Cytokines - metabolism; Host Response and Inflammation; Inflammation - metabolism; Interleukin-1beta; Lung - cytology; Lung - immunology; Lung - pathology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Monocytes - metabolism; Neutrophils - metabolism; Pneumonia - genetics; Pneumonia - immunology; Pneumonia - metabolism; Streptococcus agalactiae - immunology; Streptococcus agalactiae - pathogenicity; Tumor Necrosis Factor-alpha - metabolism; miR-223; group B streptococcus; innate immunity; inflammation
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00563-20

Group B streptococcus (GBS) is a human-pathogenic bacterium inducing a strong inflammatory response that may be detrimental for host tissues if not finely regulated. The inflammatory response can be modulated by different molecular mechanisms, among which growing evidence points toward the crucial role of microRNAs (miRNAs). Regarding innate inflammatory response, studies have reported that miR-223 is essential for the control of granulocyte proliferation and activation. Moreover, a number of investigations on miRNA expression profiling performed in various inflammatory settings have revealed that miR-223 is among the top differentially expressed miRNAs. Yet the dynamic pattern of expression of miR-223 with respect to the evolution of the inflammatory process, especially in microbial infection, remains elusive. In this study, we analyzed the kinetic expression of miR-223 in an inflammatory model of GBS-induced murine pneumonia and looked for correlates with inflammatory markers, including innate cell infiltrates. We found that miR-223 expression is rapidly induced at very early time points (3 to 6 h postinfection [p.i.]) mainly by lung-infiltrating neutrophils. Interestingly, the level of miR-223 accumulating in the lungs remains higher at later stages of infection (24 h and 48 h p.i.), and this correlates with reduced expression of primary inflammatory cytokines and chemokines and with a shift in infiltrating monocyte and macrophage subtypes toward a regulatory phenotype. Transient inhibition of miR-223 by an antagomir resulted in significant increase of CXCL2 expression and partial enhancement of infiltrating neutrophils in GBS-infected lung tissues. This suggests the potential contribution of miR-223 to the resolution phase of GBS-induced acute inflammation.