# Neutrophil heterogeneity and function in host defense during pulmonary infection

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Secondary bacterial pneumonias complicating influenza and respiratory viral infections are more severe
than primary pneumonias and often fatal, but why this occurs is unclear. Our data demonstrate that
neutrophils, which are the most abundant white blood cell and critical for fighting bacterial infections, from
influenza-infected animals display impaired ability to ingest and kill bacteria, compared to neutrophils from
uninfected and bacteria-infected animals. To date, neutrophils have been largely considered to be a
homogenous cell population, where the most important factor is whether an infected host has sufficient
numbers of neutrophils to fight infection or not. However, our preliminary data suggest that neutrophils can
adopt different subtypes - for example, our analysis of gene expression patterns of neutrophils isolated from
mouse lung following influenza or Streptococcus pneumoniae infection reveal that neutrophils from virally
infected animals ("flu-PMNs") significantly differ from neutrophils isolated from bacterially- (S. pneumoniae)
infected animals ("Sp-PMNs"), suggesting that distinct phenotypes of neutrophils emerge in the context of
different types of infection. However, neutrophil specialization is a concept that has been poorly recognized
and understood particularly in the context of infection, although studies from the cancer literature strongly
support this emerging concept. This application tests the hypothesis that neutrophils adopt distinct phenotypes
under conditions of viral (influenza) versus bacterial (S. pneumoniae) pneumonia, which is a mechanism
contributing to secondary bacterial infections. In addition, we will test the hypothesis that type I interferons,
which are a central immune mediator induced by viral infections, lead to the development of the flu-PMN
phenotype. The studies in Aim 1 will examine how viral versus bacterial infections regulate critical neutrophil
functions over time, including phagocytosis, bacterial killing, reactive oxygen species generation, neutrophil
extracellular trap formation, cytokine production, and degranulation responses. In addition, transcriptome
changes in neutrophils isolated from the bone marrow, systemic (spleen), and local (lung) compartments of
influenza versus S. pneumoniae-infected animals to determine where different neutrophil subtypes develop,
and what molecular pathways are activated that might result in different neutrophil phenotypes that emerge
during viral and bacterial infection. Finally, the expression pattern of multiple immune receptors will be
performed using a powerful novel technique, mass cytometry, to determine whether the balance between
activating and inhibitory immune receptors expressed on neutrophils govern changes in neutrophil activities.
Aim 2 will examine the in vivo mechanisms underlying how type I interferons regulate the development of the
flu-PMN phenotype, and investigate the mechanisms underlying the observation that flu-infected animals wh...

## Key facts

- **NIH application ID:** 9974284
- **Project number:** 5I01BX004565-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jane C Deng
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974284

## Citation

> US National Institutes of Health, RePORTER application 9974284, Neutrophil heterogeneity and function in host defense during pulmonary infection (5I01BX004565-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974284. Licensed CC0.

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