# Influenza regulation of epithelial pneumococcal host defense.

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $371,250

## Abstract

PROJECT SUMMARY
Influenza infection remains an international health concern despite global surveillance, effective vaccines, and
antiviral therapy. Secondary bacterial infections are emerging as an important cause of human disease to
influenza, however little is known regarding how influenza increases susceptibility to bacterial infection.
Pneumococcal infection is the most common cause of secondary bacterial infection postinfluenza, and
extrapulmonary pneumococcal infections are emerging as leading causes of acute cardiac and renal disease
in humans. Significant gaps in our knowledge around secondary pneumococcal infection exists, none larger
than the role of the lung epithelium in bacterial host defense following influenza. This application will
mechanistically deconstruct how influenza enhances susceptibility to pneumococcal infection in the lung
epithelium, and will fill important gaps in our current knowledge regarding influenza secondary bacterial
infection. Our laboratory's expertise in experimental lung infection and primary differentiated lung epithelial
culture models puts us uniquely positioned for this investigation. Here we put forth three mechanistically driven
aims supported by published and preliminary data clearly supporting our scientific premise that influenza-
driven changes in epithelial ion dysregulation confer airway surface fluid acidification that enhances
susceptibility to pneumococcal infection. Specifically, Aim 1 will elucidate the critical role of the lung epithelium
in susceptibility to pneumococci after influenza. Aim 2 will mechanistically determine epithelium ion
dysfunction leading to acidification the airway epithelial surface fluid as the underlying molecular mechanism.
Lastly, Aim 3 will elucidate the impact of increased pneumococcal infection postinfluenza in vivo in pneumonia
and disseminated extrapulmonary disease, while exploring interventions of repurposed FDA approved drugs.
Collectively, this proposal will put forth an entirely novel underlying mechanism for influenza-mediated
susceptibility to pneumococcal infection, will establish a human experimental model to study influenza-
pneumococcal coinfections, and evaluate pharmacologic interventions that could be implemented rapidly for
prophylaxis to secondary pneumococcal infections to influenza.

## Key facts

- **NIH application ID:** 10480875
- **Project number:** 5R01HL149944-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Kevin S Harrod
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2020-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480875

## Citation

> US National Institutes of Health, RePORTER application 10480875, Influenza regulation of epithelial pneumococcal host defense. (5R01HL149944-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10480875. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*