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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 Article has an altmetric score of 79

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 2

Depletion of eosinophils improves bacterial clearance and lung inflammation in the antibiotic-treated group injured with influenza followed by MRSA.

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Depletion of eosinophils improves bacterial clearance and lung inflammat...
(A and B) BAL eosinophil numbers (A) and percentages (B) in control and VNAM-treated mice infected with influenza (PR8, 250 PFU) (n = 3–4). (C) EoCre × ROSAmTmG transgenic mice were treated with control or VNAM and then injured with influenza (PR8, 250 PFU). Mice were sacrificed on day 10 after influenza infection, and lung slices were immunostained for GFP (eosinophils; green) and DAPI (blue). Image is representative of 3 different samples. Scale bars: 100 μm. (D) Mice were infected with influenza (PR8, 250 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. Mice were given intraperitoneal injections of either an isotype antibody (n = 7–10) or an anti–IL-5 antibody (n = 7–10) every 3–4 days. (E) BAL eosinophils were effectively depleted after IL-5 antibody treatment. (F and G) Total cell count (F) and PMNs (G) in the BAL were evaluated 1 and 2 days after MRSA infection (days 11 and 12, respectively). (H–K) Mice were sacrificed on day 12 and evaluated for total protein in the BAL (H), CFU of bacteria in the lungs (I), BAL IFN-γ levels (J), and BAL IL-1β levels (K). *P < 0.05, **P < 0.01, ***P < 0.001 by 2-way ANOVA.

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

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