Influenza A virus exacerbates Staphylococcus aureus pneumonia in mice by attenuating antimicrobial peptide production
Keven M Robinson1, Kevin J McHugh, Sivanarayana Mandalapu
1Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
Abstract:
Influenza A represents a significant cause of morbidity and mortality worldwide. Bacterial complications of influenza A confer the greatest risk to patients. TH17 pathway inhibition has been implicated as a mechanism by which influenza A alters bacterial host defense. Here we show that preceding influenza causes persistent Staphylococcus aureus infection and suppression of TH17 pathway activation in mice. Influenza does not inhibit S. aureus binding and uptake by phagocytic cells but instead attenuates S. aureus induced TH17 related antimicrobial peptides necessary for bacterial clearance in the lung. Importantly, exogenous lipocalin 2 rescued viral exacerbation of S. aureus infection and decreased free iron levels in the bronchoalveolar lavage from mice coinfected with S. aureus and influenza. These findings indicate a novel mechanism by which influenza A inhibits TH17 immunity and increases susceptibility to secondary bacterial pneumonia. Identification of new mechanisms in the pathogenesis of bacterial pneumonia could lead to future therapeutic targets.
Insights
Influenza A infection suppresses a key immune pathway (TH17), leading to persistent Staphylococcus aureus infections and increased risk of bacterial pneumonia in mice. Restoring lipocalin 2 levels improved bacterial clearance.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Influenza A virus is a major global health threat, often leading to severe secondary bacterial pneumonia.
- The T helper 17 (TH17) immune pathway is crucial for host defense against bacterial pathogens.
- Impaired TH17 responses are suspected in influenza-associated bacterial complications.
Purpose of the Study:
- To investigate the mechanism by which influenza A virus exacerbates Staphylococcus aureus infection.
- To determine the role of the TH17 pathway in influenza-induced susceptibility to bacterial pneumonia.
Main Methods:
- Induction of influenza A infection and Staphylococcus aureus coinfection in a mouse model.
- Assessment of TH17 pathway activation and antimicrobial peptide production.
- Analysis of bacterial burden, phagocytic cell function, and iron levels in bronchoalveolar lavage fluid.
- Administration of exogenous lipocalin 2 to evaluate its therapeutic potential.
Main Results:
- Preceding influenza A infection led to persistent Staphylococcus aureus infection and suppressed TH17 pathway activation in mice.
- Influenza A did not impair bacterial binding or uptake by phagocytes but reduced TH17-dependent antimicrobial peptides essential for bacterial clearance.
- Exogenous lipocalin 2 administration ameliorated viral exacerbation of S. aureus infection and reduced free iron in the lung.
- Influenza A infection was shown to inhibit TH17 immunity, increasing susceptibility to secondary bacterial pneumonia.
Conclusions:
- Influenza A virus establishes a novel mechanism of immune suppression by inhibiting the TH17 pathway.
- This immune dysregulation increases susceptibility to secondary Staphylococcus aureus pneumonia.
- Lipocalin 2 may play a critical role in host defense against coinfections and presents a potential therapeutic target.
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