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

dc.creatorTavares, Luciana P.
dc.creatorBrüggemann, Thayse R.
dc.creatorRezende, Rafael M.
dc.creatorMachado, Marina G.
dc.creatorCagnina, R. Elaine
dc.creatorShay, Ashley E.
dc.creatorGarcia, Cristiana
dc.creatorNijmeh, Julie
dc.creatorTeixeira, Mauro M.
dc.creatorLevy, Bruce D.
dc.date2022-10-10T11:34:32Z
dc.date2022-10-10T11:34:32Z
dc.date2022
dc.date.accessioned2023-09-26T20:51:28Z
dc.date.available2023-09-26T20:51:28Z
dc.identifierTAVARES, Luciana P. et al. Cysteinyl Maresins Reprogram Macrophages to Protect Mice from Streptococcus pneumoniae after Influenza A Virus Infection. American Society for Microbiology, v.13, n. 4, p. 1 - 16, July/August 2022.
dc.identifier2150-7511
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/55058
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8865121
dc.descriptionInfluenza 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 IAVinduced 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectVírus da gripe A
dc.subjectStreptococcus pneumoniae
dc.subjectResolução da inflamação
dc.subjectMediadores pró-resolução
dc.subjectConjugados de maresina na regeneração de tecidos (MCTRs)
dc.subjectMacrófagos alveolares
dc.subjectInfecção secundária
dc.subjectInfluenza A virus
dc.subjectStreptococcus pneumoniae
dc.subjectResolution of inflammation
dc.subjectProresolving mediators
dc.subjectMaresin conjugates in tissue regeneration (MCTRs),
dc.subjectAlveolar macrophages
dc.subjectSecondary infection
dc.titleCysteinyl Maresins Reprogram Macrophages to Protect Mice from Streptococcus pneumoniae after Influenza A Virus Infection
dc.typeArticle


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