# Control of Influenza Infection by Lipid Mediators and Macrophages

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $549,761

## Abstract

Abstract
Type A influenza virus (IAV) is a major human pathogen with the capacity to rapidly spread worldwide and to
produce severe and sometimes fatal lung infections characterized by severe pneumonia. Disease severity
resulting from IAV infection reflects the extent of virus replication in cells of the respiratory tract and the
strength or magnitude of the host innate and adaptive immune response. Thus, the host immune response is
not only responsible for IAV clearance but also contributes to tissue injury during infection. However, while the
role of immune cells in virus elimination is well documented, the role of immune cells and in particular innate
immune cells in regulating the susceptibility of respiratory tract cells in vivo to IAV infection is only poorly
understood. We recently reported in a novel mouse model of IAV infection that upregulation of the cysteinyl
leukotriene (5-lipoxygenase) metabolic pathway in terminal airway (alveolar) epithelial cells is associated with
enhanced susceptibility of these cells to IAV infection. Furthermore, terminal airway resident (alveolar)
macrophages suppress the upregulation of the 5-lipoxygenase pathway in terminal airway epithelial cells and
as a consequence reduce the susceptibility of the cells to IAV infection. The program described in this
application is designed to explore the role of the 5-lipoxygenase metabolic pathway and signaling via cysteinyl
leukotriene receptors in controlling the susceptibility of airway epithelial cells to IAV infection and the
mechanism by which terminal airway macrophages reduce susceptibility. We will establish the requirement for
5-lipoxygenase pathway enzymatic activity, cysteinyl leukotriene receptor signaling in terminal airway epithelial
cells and explore the mechanism by which signaling through this receptor enhances susceptibility to IAV
infection (Aim 1). In conjunction, we will explore the interaction between terminal airway macrophages, airway
epithelial cells and IAV resulting in suppression of susceptibility of airway epithelial cells to infection, the
mechanism of macrophage action leading to suppression and extend this analysis into the human (Aim 2).

## Key facts

- **NIH application ID:** 10074518
- **Project number:** 5R01AI136297-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Thomas J Braciale
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,761
- **Award type:** 5
- **Project period:** 2018-01-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074518

## Citation

> US National Institutes of Health, RePORTER application 10074518, Control of Influenza Infection by Lipid Mediators and Macrophages (5R01AI136297-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074518. Licensed CC0.

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