# Role of stearoyl-CoA desaturase 2 in macrophage-mediated antimicrobial immunity

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2022 · $32,686

## Abstract

ABSTRACT
Urinary tract infections (UTIs) predominantly caused by uropathogenic E. coli (UPEC) have a high rate of
recurrence in elderly women, a major health problem. Though there are many factors that contribute to this
increased susceptibility, age-related changes in macrophage function may also play a role. Macrophages are
innate immune cells that are recruited as first responders to help control infection by: recognizing and
internalizing pathogens for degradation; presenting antigens to recruit the adaptive immune response; and
orchestrating tissue inflammation. Previous studies have demonstrated that macrophages become dysfunctional
with age due in part to perturbations in lipid homeostasis. For instance, the fatty acid-desaturating enzyme
stearoyl-CoA desaturase 2 (SCD2) becomes downregulated with age. However, the role of SCD2 in maintaining
macrophage functions in infection is not clearly understood. Preliminary data indicate that SCD2-deficient
macrophages are less able to eliminate internalized UPEC, perhaps due to deficits in autophagosome
degradation and mitochondrial function. A model is proposed by which deficiency of SCD2 alters the lipid
composition of cellular membranes thereby disrupting membrane-dependent processes, such as
autophagosome fusion with lysosomes for degradation or cellular respiration across the inner mitochondrial
membrane. Therefore, aim 1 will study SCD2-deficient macrophages in vitro to further elucidate these defective
cellular and molecular processes that increase susceptibility to UPEC infection. Aim 2 will determine whether
macrophage SCD2 plays an important role in the host response to UPEC infection in a mouse model of UTI.
Completion of this study will provide a deeper understanding of the mechanism by which SCD2-mediated lipid
metabolism maintains fundamental macrophage immune functions, an important knowledge gap that remains in
the field, as well as expand on the existing understanding of lipid metabolism in macrophages and aging.
Additionally, this work may reveal novel strategies for the clinical management of recurrent UTIs in the elderly,
for which treatments remain inadequate. Together with a student-focused training plan and rigorous but
collaborative research environment, the proposed study will also enable the PI to extend existing and acquire
new technical, scientific, and professional skills that will be key to becoming an independent investigator. To
further enhance training, a strategy is included to integrate clinical activities and prepare the PI for transitioning
to the next stage of their career.

## Key facts

- **NIH application ID:** 10469988
- **Project number:** 5F30DK130282-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Joseph B Lin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,686
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469988

## Citation

> US National Institutes of Health, RePORTER application 10469988, Role of stearoyl-CoA desaturase 2 in macrophage-mediated antimicrobial immunity (5F30DK130282-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10469988. Licensed CC0.

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