# Innate Immunity in Lung Infection-induced Sepsis

> **NIH NIH R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2022 · $585,488

## Abstract

SUMMARY
Pulmonary infections are a leading cause of sepsis/septicemia that poses substantial mortality and long-
term morbidity and health care costs. Successful clearance of pathogens from the respiratory tract is
dependent on effective innate immune responses. Understanding the innate immune mechanisms in the
pulmonary system is critical for better immunotherapeutics or vaccines. The signaling cascades triggering
innate immune responses consist of a delicate balance between pro-inflammatory signaling cascades,
and counteracting anti-inflammatory signaling. However, it is not quite clear how these innate immune
cascades converge to augment clear pathogens while reducing tissue damage. To explore the host
defense cascades, we have focused on a primary gram-negative extracellular pathogen, Klebsiella
pneumoniae since this bacterium induces severe lung infection followed by sepsis; multiple drug-resistant
strains have recently emerged; and no effective vaccine is available. The proposal will use 4 specific aims
to test the overall hypothesis: NLRP10 is a critical regulator of a host defense pathway through IL-17A
that can be targeted for prevention or treatment. The first aim will explore if activation of NLRP10
augments bacterial clearance and neutrophil recruitment and function. The second aim will study if the
NLRP10-dependent IL-17 production enhances host defense. The third aim will examine if NLRP10
disruption causes functional alterations in alveolar macrophages. The fourth aim will investigate if
augmentation of NLRP10 signaling can enhance host defense against K. pneumoniae. We anticipate this
proposal using a unique combination of in vivo and in vitro systems, including KO mice, overexpression,
and adoptive transfer strategies will enhance our understanding of the mechanisms by which NLRP10
modulates pulmonary host defense in both physiologic and pathologic conditions.

## Key facts

- **NIH application ID:** 10163792
- **Project number:** 5R01AI140500-04
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Samithamby Jeyaseelan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $585,488
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163792

## Citation

> US National Institutes of Health, RePORTER application 10163792, Innate Immunity in Lung Infection-induced Sepsis (5R01AI140500-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163792. Licensed CC0.

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