# Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $506,378

## 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 even
in previously healthy individuals. Further, secondary bacterial pneumonia with Staphylococcus aureus is
increasing in prevalence and is now more common than Streptococcus pneumoniae, the previously
predominant pathogen. The lack of effective anti-viral therapeutics, immunomodulatory drugs, and increasing
antibiotic resistance, coupled with poor vaccine coverage and efficacy, results in a dire need for novel
therapeutic target identification. The focus of this application is upon understanding the influenza-induced
mechanisms of susceptibility to bacterial super-infection, the leading cause of death during seasonal and
pandemic outbreaks. During the previous funding periods, 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 this area, elucidating aberrant host defense pathways in this context. In this
application, we will build upon our ongoing work with two highly novel Aims derived from the original focus. We
now provide preliminary data implicating a detrimental role for type III interferon (IFNλ) in super-infection
through inhibiting monocyte function and pattern recognition receptor expression. These data support the
hypothesis that influenza induced IFNλ directly inhibits monocyte antibacterial function via suppression of
SIGNR3/4, which is required for subsequent activation of Type 17 immunity and S. aureus clearance during
super-infection. In Aim 1, we will determine the mechanism by which IFNλ inhibits monocyte function during
influenza, S. aureus super-infection. In Aim 2, we will define the role of SIGNR3/4 in host defense against S.
aureus in the lung. The proposed studies will further our understanding of how influenza impairs subsequent
immunity against S. aureus (Aim 1) and how the immune response to influenza attenuate S. aureus clearance
in the lung (Aim 2). Our overriding goal is to understand the critical mechanism(s) of susceptibility to influenza,
S. aureus super-infection and identify novel treatment targets in a pre-clinical model of disease.

## Key facts

- **NIH application ID:** 10206840
- **Project number:** 2R01HL107380-10A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** John F Alcorn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,378
- **Award type:** 2
- **Project period:** 2012-01-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206840

## Citation

> US National Institutes of Health, RePORTER application 10206840, Influenza A Inhibits TH17 Host Defense Against Bacterial Pneumonia (2R01HL107380-10A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10206840. Licensed CC0.

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