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Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial
Marilia Sanches Santos Rizzo Zuttion1,2, Tanyalak Parimon1,2, Stephanie A Bora1,2
1Department of Medicine.
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.
Insights
Antibiotic use during influenza impairs lung immunity, increasing secondary bacterial infection risk. This study reveals antibiotics promote eosinophils, hindering immune response and worsening patient outcomes.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Secondary bacterial pneumonia is a major cause of death after influenza.
- Antibiotic use for viral infections is common despite lacking indication.
- Antibiotics may negatively impact immune defenses during viral illnesses.
Purpose of the Study:
- To investigate the immunologic consequences of antibiotic use during influenza infection.
- To determine the role of eosinophils in antibiotic-induced immune impairment.
- To assess the clinical relevance of these findings in hospitalized patients.
Main Methods:
- Murine model of influenza infection and secondary Staphylococcus aureus challenge.
- Assessment of lung immune cell populations, including eosinophils and macrophages.
- Analysis of fungal dysbiosis and its impact on host defense.
- Retrospective analysis of patient cohorts correlating antibiotic use, eosinophilia, and clinical outcomes.
Main Results:
- Antibiotic treatment during influenza infection impaired innate lung immunity against methicillin-resistant Staphylococcus aureus (MRSA).
- Antibiotics increased lung eosinophils, which inhibited macrophage function via major basic protein.
- Antibiotic-induced fungal dysbiosis promoted lung eosinophilia and reduced MRSA clearance.
- In patients, eosinophil levels correlated with antibiotic use, inflammation, and poorer outcomes.
Conclusions:
- Antibiotic administration during influenza infection has detrimental immunologic effects.
- Eosinophil recruitment to the lungs, driven by antibiotic use, increases susceptibility to secondary bacterial infections.
- Findings highlight the risks of non-indicated antibiotic use during viral respiratory illnesses.
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