# Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $391,250

## Abstract

SUMMARY
Pneumonia, caused by bacterial and/or viral etiology, is the leading cause of death in children worldwide.
Preceding viral illness, linked to influenza infection, is a primary risk factor associated with secondary bacterial
pneumonia. Influenza infection is an annual, seasonal cause of morbidity and mortality throughout the world.
Severe influenza pneumonia is often exacerbated by bacterial infection resulting in poor patient outcomes in
those with preexisting lung morbidity and in previously healthy individuals. The pandemic potential of influenza
viruses heightens the importance of understanding disease pathogenesis. Further, secondary bacterial
pneumonia with Staphylococcus aureus is increasing in prevalence, while antibiotic resistance continues to
propagate. The focus of this application is upon understanding the influenza-induced mechanisms of
susceptibility to bacterial super-infection, the leading cause of death during pandemic outbreaks. During the
previous funding period, our laboratory has identified suppression of bacterial-induced Type 17 immune
responses by preceding influenza as a critical susceptibility mechanism. We have published extensively in the
area of elucidating aberrant host defense pathways in this context. In this renewal application, we will build
upon our ongoing work with three highly novel Aims derived from the original focus. We hypothesize that S.
aureus-induced Type 17 innate immune activation is negatively regulated by influenza-induced STAT2
signaling and the Asc inflammasome. Further, we propose that exogenous antimicrobial peptide (AMP) therapy
presents a novel therapeutic strategy in influenza, bacterial super-infection. In Aim 1 we will determine the
mechanism(s) by which STAT2 signaling impairs anti-bacterial host defense against S. aureus during influenza
super-infection. Aim 2 will focus on the mechanism(s) by which Asc inflammasome knockout mice are
protected from exacerbation of secondary S. aureus infection. In Aim 3 we will investigate the mechanism of
AMP production and evaluate the therapeutic potential of exogenous AMPs during influenza, S. aureus super-
infection. The proposed studies will further our understanding of how influenza impairs subsequent immunity
against S. aureus (Aim 1), how the immune response to S. aureus is initiated in the lung (Aim 2), and test
novel therapeutic approaches for controlling post-influenza secondary bacterial pneumonia (Aim 3). Our
overriding goal is to understand the critical mechanism(s) of susceptibility to influenza, S. aureus super-
infection and provide novel treatment targets in a pre-clinical model of disease.

## Key facts

- **NIH application ID:** 9893010
- **Project number:** 5R01HL107380-09
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** John F Alcorn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2012-01-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893010

## Citation

> US National Institutes of Health, RePORTER application 9893010, Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia (5R01HL107380-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893010. Licensed CC0.

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