# ILC2-Mediated Protection from Acute Lung Infection

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2020 · $469,445

## Abstract

Project Summary
There is only limited information about the newly described type 2 innate lymphoid cell (ILC2) population in the
lung, the regulation of these cells, and their impact on protection against acute respiratory infections. We have
now found that IFN-γ negatively regulates ILC2 immune function and that animals deficient in IFN-γ expression
demonstrate increased resistance to both primary H1N1 pandemic virus infection as well as secondary
pneumococcal infection. Enhanced ILC2 activity in viral-infected IFN-γ-/- mice is accompanied by decreased
lung tissue inflammation and increased expression of pulmonary IL-5, amphiregulin, and eosinophils, but no
change in viral burden. Importantly, the increased protection seen after IFN-γ neutralization is not observed in
ILC2-deficient mice. Studies in this proposal are designed to now determine the unique role of ILC2s in
resistance to influenza and secondary bacterial infections. Based on our preliminary data, we hypothesize
that IFN-γ signaling diminishes ILC2 innate effector function and leads to decreased tissue
homeostasis and host survival. To test this concept, we will exploit several unique resources, including
novel strains of mice that are deficient in ILC2s, eosinophil expression, and TGF-βIIR signaling, as well as our
extensive experience in studying host-pathogen interactions. The aims are to determine for the first time: 1)
the role of ILC2s in mediating resistance to CA04 influenza infection; and 2) the role of ILC2s in regulating
susceptibility to secondary bacterial infections following influenza. The ultimate goal is to obtain an
understanding of the processes responsible for protection against acute respiratory infection and to exploit the
information obtained in order to influence clinical approaches for prevention and treatment of influenza and
associated secondary bacterial infections.

## Key facts

- **NIH application ID:** 9836879
- **Project number:** 5R01HL140496-03
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** DENNIS W METZGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,445
- **Award type:** 5
- **Project period:** 2017-12-12 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836879

## Citation

> US National Institutes of Health, RePORTER application 9836879, ILC2-Mediated Protection from Acute Lung Infection (5R01HL140496-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836879. Licensed CC0.

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