# Influenza Attenuates Innate Pulmonary Host Defense against Invasive Pulmonary Aspergillosis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $510,570

## Abstract

PROJECT SUMMARY
Fungal pathogens are a serious threat to human health. Invasive pulmonary aspergillosis (IPA) is a severe, life-
threatening disease that occurs when Aspergillus fumigatus (AF) spores are inhaled into the respiratory tract
and invade airway or lung tissue. More than 200,000 cases of invasive aspergillosis occur each year. A newly
identified risk factor for IPA in critically ill patients is influenza infection. Influenza is a common respiratory illness
that affects 5-20% of the population each year. Our long-term goal is to develop novel therapeutic interventions
for use in clinical settings to prevent morbidity and mortality from IPA. The focus of this application is to identify
cell signaling pathways that increase susceptibility to invasive fungal disease following influenza infection. Our
preliminary data support that preceding influenza inhibits neutrophil recruitment to the lung, in contrast to post-
bacterial pneumonia, and neutropenia is a key risk factor for the development of IPA. Additionally, preceding
influenza inhibits neutrophil function against secondary AF infection. Furthermore, our preliminary data
demonstrate that the pathogen recognition receptor, CD209a, is decreased in post-influenza IPA, suggesting
that preceding influenza may inhibit fungal-sensing. Based on our preliminary data, we hypothesize that
preceding influenza A infection limits innate immunity and increases susceptibility to invasive pulmonary
aspergillosis by inhibiting CD209a and reducing the host response to secondary Aspergillus fumigatus infection
in the lung, including neutrophil recruitment and function. Our research aims include 1) Determine whether
neutrophil recruitment and effector functions are inhibited in post-influenza IPA, and 2) Determine whether
suppression of CD209a-dependent AF sensing promotes post-influenza IPA. The proposed studies will increase
our understanding of how influenza inhibits neutrophil migration to and function within the lung in response to
subsequent AF infection (Aim1) and how the immune response to AF is initiated in the lung (Aim 2).

## Key facts

- **NIH application ID:** 10297248
- **Project number:** 1R01AI153337-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Keven Mara Robinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $510,570
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297248

## Citation

> US National Institutes of Health, RePORTER application 10297248, Influenza Attenuates Innate Pulmonary Host Defense against Invasive Pulmonary Aspergillosis (1R01AI153337-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10297248. Licensed CC0.

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