Cysteinyl Maresins Reprogram Macrophages to Protect Mice from Streptococcus pneumoniae after Influenza A Virus Infection.

Autor:	P Tavares L; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, Minas Gerais, Brazil., Brüggemann TR; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., M Rezende R; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., G Machado M; Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, Minas Gerais, Brazil., Cagnina RE; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Shay AE; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., C Garcia C; Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brazil., Nijmeh J; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., M Teixeira M; Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, Minas Gerais, Brazil., Levy BD; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2022 Aug 30; Vol. 13 (4), pp. e0126722. Date of Electronic Publication: 2022 Aug 01.
DOI:	10.1128/mbio.01267-22
Abstrakt:	Influenza A virus (IAV) infections are a leading cause of mortality worldwide. Excess mortality during IAV epidemics and pandemics is attributable to secondary bacterial infections, particularly pneumonia caused by Streptococcus pneumoniae. Resident alveolar macrophages (rAMs) are early responders to respiratory infections that coordinate initial host defense responses. Maresin conjugates in tissue regeneration (MCTRs) are recently elucidated cysteinyl maresins that are produced by and act on macrophages. Roles for MCTRs in responses to respiratory infections remain to be determined. Here, IAV infection led to transient decreases in rAM numbers. Repopulated lung macrophages displayed transcriptional alterations 21 days post-IAV with prolonged susceptibility to secondary pneumococcal infection. Administration of a mix of MCTR1 to 3 or MCTR3 alone post-IAV decreased lung inflammation and bacterial load 48 and 72 h after secondary pneumococcal infection. MCTR-exposed rAMs had increased migration and phagocytosis of Streptococcus pneumoniae, reduced secretion of CXCL1, and a reversion toward baseline levels of several IAV-induced pneumonia susceptibility genes. Together, MCTRs counter regulated post-IAV changes in rAMs to promote a rapid return of bacteria host defense. IMPORTANCE Secondary bacterial pneumonia is a serious and common complication of IAV infection, leading to excess morbidity and mortality. New host-directed approaches are needed to complement antibiotics to better address this important global infectious disease. Here, we show that harnessing endogenous resolution mechanisms for inflammation by exogenous administration of a family of specialized proresolving mediators (i.e., cys-MCTRs) increased macrophage resilience mechanisms after IAV to protect against secondary infection from Streptococcus pneumoniae.
Databáze:	MEDLINE
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