Antiviral epithelial-macrophage crosstalk permits secondary bacterial infections.

Autor: Lane S; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., White TLA; Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., Walsh EE; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., Cattley RT; Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., Cumberland R; Tumor Microenvironment Center, UPMC Hillman Cancer Center , Pittsburgh, Pennsylvania, USA., Hawse WF; Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., Delgoffe GM; Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.; Tumor Microenvironment Center, UPMC Hillman Cancer Center , Pittsburgh, Pennsylvania, USA., Badylak SF; McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania, USA.; Department of Surgery, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.; Department of Bioengineering, University of Pittsburgh Swanson School of Engineering , Pittsburgh, Pennsylvania, USA., Bomberger JM; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: MBio [mBio] 2023 Oct 31; Vol. 14 (5), pp. e0086323. Date of Electronic Publication: 2023 Sep 29.
DOI: 10.1128/mbio.00863-23
Abstrakt: Importance: Miscommunication of antiviral and antibacterial immune signals drives worsened morbidity and mortality during respiratory viral-bacterial coinfections. Extracellular vesicles (EVs) are a form of intercellular communication with broad implications during infection, and here we show that epithelium-derived EVs released during the antiviral response impair the antibacterial activity of macrophages, an innate immune cell crucial for bacterial control in the airway. Macrophages exposed to antiviral EVs display reduced clearance of Staphylococcus aureus as well as altered inflammatory signaling and anti-inflammatory metabolic reprogramming, thus revealing EVs as a source of dysregulated epithelium-macrophage crosstalk during coinfection. As effective epithelium-macrophage communication is critical in mounting an appropriate immune response, this novel observation of epithelium-macrophage crosstalk shaping macrophage metabolism and antimicrobial function provides exciting new insight and improves our understanding of immune dysfunction during respiratory coinfections.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE