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Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia
Marilia Sanches Santos Rizzo Zuttion, … , David M. Underhill, Peter Chen
Marilia Sanches Santos Rizzo Zuttion, … , David M. Underhill, Peter Chen
Published September 10, 2024
Citation Information: J Clin Invest. 2024;134(21):e180986. https://doi.org/10.1172/JCI180986.
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Research Article Infectious disease Pulmonology

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia

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Abstract

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

Marilia Sanches Santos Rizzo Zuttion, Tanyalak Parimon, Stephanie A. Bora, Changfu Yao, Katherine Lagree, Catherine A. Gao, Richard G. Wunderink, Georgios D. Kitsios, Alison Morris, Yingze Zhang, Bryan J. McVerry, Matthew E. Modes, Alberto M. Marchevsky, Barry R. Stripp, Christopher M. Soto, Ying Wang, Kimberly Merene, Silvia Cho, Blandine L. Victor, Ivan Vujkovic-Cvijin, Suman Gupta, Suzanne L. Cassel, Fayyaz S. Sutterwala, Suzanne Devkota, David M. Underhill, Peter Chen

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Figure 1

Antibiotic treatment of mice during influenza infection impairs bacterial clearance and augments lung inflammation after a subsequent challenge with MRSA.

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Antibiotic treatment of mice during influenza infection impairs bacteria...
(A) Mice were infected with influenza (PR8, 500 PFU) at day 0 followed by MRSA at day 10. Control or antibiotics (VNAM) were started 7 days before PR8 infection to allow mice to equilibrate to the treatment and discontinued at day 7 to allow it to wash out before MRSA challenge. (B) Weight relative to that at day 10 showed a slower recovery after MRSA challenge in the VNAM-treated group (n = 18) compared with control (n = 31) at days 11 and 12 (1 and 2 days after MRSA infection, respectively). (C) Representative images from 3 different H&E-stained lungs at day 11 of the 2-hit model. Scale bars: 2 mm (left), 500 μm (right). (D–I) Mice were sacrificed on day 12 after the 2-hit infection; the lungs were evaluated for CFU of bacteria (n = 26 and 21 for control and VNAM groups, respectively) (D), and BAL was evaluated for IFN-γ levels (n = 13 and 12 for control and VNAM groups, respectively) (E), total cell count (n = 26 and 21 for control and VNAM groups, respectively) (F), PMN count (n = 13 and 12 for control and VNAM groups, respectively) (G), macrophages (n = 9 and 8 for control and VNAM groups, respectively) (H), and eosinophils (n = 12 and 13 for control and VNAM groups, respectively) (I). *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.0001 by 2-tailed Student’s t test.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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