Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia
A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection.
Authors
- Tanyalak Parimon (ORCID: https://orcid.org/0000-0002-4790-0730)
- Changfu Yao (ORCID: https://orcid.org/0000-0003-1357-5017)
- Alberto M. Marchevsky (ORCID: https://orcid.org/0000-0003-1467-0710)
- Suzanne Devkota (ORCID: https://orcid.org/0000-0001-5575-9362)
- David M. Underhill (ORCID: https://orcid.org/0000-0002-2989-658X)
- Marilia Sanches Santos Rizzo Zuttion (ORCID: https://orcid.org/0000-0002-0185-9074)
- Silvia Cho
- Fayyaz S. Sutterwala (ORCID: https://orcid.org/0000-0002-7338-3095)
- Ivan Vujkovic-Cvijin (ORCID: https://orcid.org/0000-0002-8611-4900)
- Richard G. Wunderink (ORCID: https://orcid.org/0000-0002-8527-4195)
- Matthew Modes (ORCID: https://orcid.org/0000-0002-1568-1393)
- Catherine A. Gao (ORCID: https://orcid.org/0000-0001-5576-3943)
- Barry R. Stripp (ORCID: https://orcid.org/0000-0003-4348-2137)
- Georgios D. Kitsios (ORCID: https://orcid.org/0000-0002-1018-948X)
- Bryan J. McVerry (ORCID: https://orcid.org/0000-0002-1175-4874)
- Christopher M. Soto (ORCID: https://orcid.org/0009-0001-3425-8056)
- Suzanne L. Cassel
- Ying Wang
- Peter Chen (ORCID: https://orcid.org/0000-0002-5330-1718)
- Yingze Zhang (ORCID: https://orcid.org/0000-0001-6947-2901)
- Alison Morris (ORCID: https://orcid.org/0000-0002-7290-6536)
- Katherine Lagree (ORCID: https://orcid.org/0000-0003-1430-3312)
- Suman Gupta (ORCID: https://orcid.org/0000-0001-7293-7423)
- Kimberly Merene
- Stephanie A. Bora
- Blandine Victor
Institutions
- Northwestern University (US)
- Cedars-Sinai Medical Center (US)
- Institute for Women's Policy Research (US)
- University of Pittsburgh (US)
- The Ojai Foundation (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2024-09-10
- DOI
- https://doi.org/10.1172/jci180986
- Citations
- 8
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 3.09
Funders
- NIH Office of the Director