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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 78

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 6

Cotreatment with fluconazole improves bacterial clearance and reverses the worsened lung injury in antibiotic-treated mice.

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Cotreatment with fluconazole improves bacterial clearance and reverses t...
(A) Mice were infected with influenza (PR8, 250 PFU) at day 0 followed by MRSA at day 10. Control, antibiotics alone (VNAM), or VNAM and cotreatment with fluconazole (VNAM+Fluco) 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 on day 10 showed slower recovery after MRSA challenge in the VNAM-treated group (n = 22) compared with control (n = 21) and VNAM+Fluco (n = 13) groups at days 11 and 12 (1 and 2 days after MRSA infection, respectively) by 2-way ANOVA. ****P < 0.0001 in post hoc analysis at day 12. (C–L) Mice in control (C), VNAM (V), and VNAM+Fluco (VF) groups were injured in the 2-hit model and sacrificed for evaluation of (C) day 11 BAL total cell count (C: n = 9; V: n = 10; VF: n = 10); (D) day 12 BAL cell count (C: n = 22; V: n = 15; VF: n = 10); (E) day 10 BAL eosinophil count (C: n = 5; V: n = 4; VF: n = 3); (F) day 11 BAL eosinophil count (C: n = 26; V: n = 24; VF: n = 8); (G) day 12 BAL eosinophil count (C: n = 13; V: n = 12; VF: n = 9); (H) day 10 lung MBP-1 levels (C: n = 4; V: n = 4; VF: n = 5); (I) day 12 BAL IFN-γ levels (C: n = 4; V: n = 4; VF: n = 5); (J) day 12 BAL IL-1β levels (C: n = 4; V: n = 4; VF: n = 5); (K) day 11 lung MRSA CFU (C: n = 9; V: n = 10; VF: n = 9); and (L) day 12 lung MRSA CFU (C: n = 27; V: n = 21; VF: n = 8). (C–L) One-way ANOVA with post hoc analysis was used to determine P values within the respective panels. ANOVA P values are listed in each panel. Post hoc comparisons are represented as follows: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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

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