# Obesity Inhibits Innate Lung Bactericidal Functions

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $39,112

## Abstract

Project Abstract
Obesity is a major global public health concern. Worldwide, 39% of the population is overweight and 13% of the
population is obese. Obesity contributes to many other diseases, such as heart disease, stroke, some cancers,
and notably, type 2 diabetes (T2D). Currently, 425 million people globally have been diagnosed with T2D and
this number is expected to grow to over 600 million people by 2050. Although T2D itself is a non-communicable
disease, many patients with diabetes are more susceptible to microbial infections and exhibit a higher burden of
disease. Although obese animals have an increased production of myeloid cells, previous work from our labs
has shown that a failure to heal diabetic wounds corresponds to elevated levels of prostaglandin E2 (PGE2) in
the inflammatory macrophages that are recruited to the wound. Furthermore, past studies from our lab have
demonstrated that PGE2 signaling can impair the innate immune functions of macrophages. Therefore, we
hypothesized that diabetic obese mice would be more susceptible to a respiratory Pseudomonas aeruginosa
strain PA01 infection due to impaired function of lung resident and recruited macrophages. Preliminary studies
demonstrate that obese diabetic mice do have an increased P. aeruginosa burden in the lung 24 hours after
infection. Additionally, we have determined that naïve obese diabetic mice have an increase in lung neutrophils
compared to lean mice, however, after infection with P. aeruginosa, these mice have a decrease in neutrophils
compared to lean mice. This suggests that obese mice have a defect in neutrophil recruitment during infection.
Additionally, neutrophil function assays show that neutrophils from obese diabetic mice have a defect in killing
P. aeruginosa. These observations drive this proposal which will test the hypothesis that obese diabetic mice
have not only a defect in innate immune cell recruitment, but also a defect in innate immune cell function during
bacterial pneumonia. This hypothesis will be tested through two specific aims: Aim 1) determine the functional
defects in alveolar macrophages during P. aeruginosa infection and Aim 2) determine the bacterial clearance
and recruitment defects in neutrophils during P. aeruginosa infection. Throughout these aims, we explore sex
as a biological variable, as males have enhanced obesity-induced inflammation compared to females.
Experiments for these aims will be completed with the use of a murine diet induced obesity model, cells derived
from these mice, and human cells derived from discarded blood samples from patients with and without T2D.
The results from these innovative studies may inform treatments to improve outcomes from bacterial pneumonia
in patients with T2D. Completion of this proposal will also allow for the applicant to receive rigorous training in
experimental design, implementation, and interpretation that will help her become a successful, independent
scientist.

## Key facts

- **NIH application ID:** 10462029
- **Project number:** 1F31HL163865-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gabrielle Entrup
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,112
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462029

## Citation

> US National Institutes of Health, RePORTER application 10462029, Obesity Inhibits Innate Lung Bactericidal Functions (1F31HL163865-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462029. Licensed CC0.

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