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IFN-γ Drives TNF-α Hyperproduction and Lethal Lung Inflammation during Antibiotic Treatment of Postinfluenza Staphylococcus aureus Pneumonia.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Sep 01; Vol. 207 (5), pp. 1371-1376. Date of Electronic Publication: 2021 Aug 11. - Publication Year :
- 2021
-
Abstract
- Inflammatory cytokine storm is a known cause for acute respiratory distress syndrome. In this study, we have investigated the role of IFN-γ in lethal lung inflammation using a mouse model of postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. To mimic the clinical scenario, animals were treated with antibiotics for effective bacterial control following MRSA superinfection. However, antibiotic therapy alone is not sufficient to improve survival of wild-type animals in this lethal acute respiratory distress syndrome model. In contrast, antibiotics induce effective protection in mice deficient in IFN-γ response. Mechanistically, we show that rather than inhibiting bacterial clearance, IFN-γ promotes proinflammatory cytokine response to cause lethal lung damage. Neutralization of IFN-γ after influenza prevents hyperproduction of TNF-α, and thereby protects against inflammatory lung damage and animal mortality. Taken together, the current study demonstrates that influenza-induced IFN-γ drives a stepwise propagation of inflammatory cytokine response, which ultimately results in fatal lung damage during secondary MRSA pneumonia, despite of antibiotic therapy.<br /> (Copyright © 2021 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Cells, Cultured
Humans
Influenza, Human complications
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections complications
Pneumonia, Staphylococcal complications
Staphylococcal Infections complications
Superinfection
Tumor Necrosis Factor-alpha
Anti-Bacterial Agents therapeutic use
Inflammation immunology
Influenza A virus physiology
Influenza, Human immunology
Interferon-gamma metabolism
Lung immunology
Orthomyxoviridae Infections immunology
Pneumonia, Staphylococcal immunology
Staphylococcal Infections immunology
Staphylococcus aureus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 207
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 34380647
- Full Text :
- https://doi.org/10.4049/jimmunol.2100328