Severe influenza infection is associated with inflammatory programmed cell death in infected macrophages.

Autor:	Ferreira AC; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; Preclinical Research Laboratory, Universidade Iguaçu (UNIG), Nova Iguaçu, RJ, Brazil., Sacramento CQ; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Pereira-Dutra FS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Fintelman-Rodrigues N; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Silva PP; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; Preclinical Research Laboratory, Universidade Iguaçu (UNIG), Nova Iguaçu, RJ, Brazil., Mattos M; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., de Freitas CS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Marttorelli A; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., de Melo GR; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Campos MM; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Azevedo-Quintanilha IG; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Carlos AS; Preclinical Research Laboratory, Universidade Iguaçu (UNIG), Nova Iguaçu, RJ, Brazil., Emídio JV; Preclinical Research Laboratory, Universidade Iguaçu (UNIG), Nova Iguaçu, RJ, Brazil., Garcia CC; Respiratory and Measles Virus Laboratory, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Bozza PT; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil., Bozza FA; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute of Infectious Disease Evandro Chagas, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; Department of Critical Care, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brazil., Souza TML; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswado Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Feb 16; Vol. 13, pp. 1067285. Date of Electronic Publication: 2023 Feb 16 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1067285
Abstrakt:	Introduction: Influenza A virus (IAV) is one of the leading causes of respiratory tract infections in humans, representing a major public health concern. The various types of cell death have a crucial role in IAV pathogenesis because this virus may trigger both apoptosis and necroptosis in airway epithelial cells in parallel. Macrophages play an important role in the clearance of virus particles, priming the adaptive immune response in influenza. However, the contribution of macrophage death to pathogenesis of IAV infection remains unclear. Methods: In this work, we investigated IAV-induced macrophage death, along with potential therapeutic intervention. We conducted in vitro and in vivo experiments to evaluate the mechanism and the contribution of macrophages death to the inflammatory response induced by IAV infection. Results: We found that IAV or its surface glycoprotein hemagglutinin (HA) triggers inflammatory programmed cell death in human and murine macrophages in a Toll-like receptor-4 (TLR4)- and TNF-dependent manner. Anti-TNF treatment in vivo with the clinically approved drug etanercept prevented the engagement of the necroptotic loop and mouse mortality. Etanercept impaired the IAV-induced proinflammatory cytokine storm and lung injury. Conclusion: In summary, we demonstrated a positive feedback loop of events that led to necroptosis and exacerbated inflammation in IAV-infected macrophages. Our results highlight an additional mechanism involved in severe influenza that could be attenuated with clinically available therapies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ferreira, Sacramento, Pereira-Dutra, Fintelman-Rodrigues, Silva, Mattos, de Freitas, Marttorelli, de Melo, Campos, Azevedo-Quintanilha, Carlos, Emídio, Garcia, Bozza, Bozza and Souza.)
Databáze:	MEDLINE
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