# Genetic susceptibility to mucosal infections with aging (Resubmission)

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $199,375

## Abstract

Project Summary/Abstract
Aging is strongly associated with increased mortality and morbidity following bacterial infections, which are
responsible for one third of all deaths in older adults. The two most common infections in older adults are
pneumonia and urinary tract infection (UTI), both of which occur at mucosal surfaces and are prevalent across
the lifespan but exhibit an age-dependent increase in disease severity. The age-dependent severity of these
infections is thought to be driven by disruptions in immune responses, including decline in immune cell function
(immunosenescence) and chronic low-grade inflammation (inflammaging). While age-driven alterations in
adaptive immune responses are well characterized, less is known about what drives innate
immunosenescence. Polymorphonuclear leukocytes (PMNs) are innate immune cells that have a critical and
multi-faceted role in control of mucosal infection and subsequent return to homeostasis, and PMN function and
recruitment are both dysregulated during aging, further contributing to infection susceptibility and severity.
Accordingly, genetic polymorphisms that impact PMN recruitment and activation in response to infection are
associated with increased infection susceptibility and severity. However, there is fundamental gap in
knowledge regarding genetic traits that may be associated with protection against age-driven susceptibility to
infection. The hypothesis of this proposal is that certain genetic loci will be associated with protection against
severe disease following mucosal infection, and that some of these protective phenotypes may be resistant to
age-driven deterioration. This hypothesis will be addressed through two specific aims. In Aim 1, 25 CC strains
and a C57BL/6J founder strain that exhibits a susceptible phenotype will be assessed for susceptibility to
pneumonia (males) and UTI (females). Host survival, organ-specific bacterial burden, indicators of infection
severity (such as organ pathology) and inflammatory responses will be measured to determine which
phenotypes are linked for a given infection model. Linked phenotypes will be used to identify QTLs associated
with disease manifestation for each infection model, and phenotypes in common between both infection
models will be explored as predictors of infection severity. In Aim 2, C57BL/6 and a subset of 3 CC strains that
exhibit resistant phenotypes in youth will be aged and assessed for susceptibility to pneumonia (males) and
UTI (females). The above indicators of disease manifestation will be assessed to determine if host genetics
can alleviate age-driven susceptibility to mucosal infections. The proposed research is expected to yield a
wealth of phenomic data, information pertaining to immune system development and function during
homeostasis and in response to antigenic challenge at all stages of life, and the utility of urine and serum
cytokines and chemokines as potential biomarkers to predict infection susceptibility and...

## Key facts

- **NIH application ID:** 10172840
- **Project number:** 5R21AI145370-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Chelsie Elizabeth Armbruster
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,375
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172840

## Citation

> US National Institutes of Health, RePORTER application 10172840, Genetic susceptibility to mucosal infections with aging (Resubmission) (5R21AI145370-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10172840. Licensed CC0.

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