# Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $451,775

## Abstract

ABSTRACT
 This application proposes to interrogate how the divalent cation transporter NRAMP1/SLC11A1 mediates
control of infection with bacterial pathogens. While the function of this transporter has been studied in
macrophages, our studies on the link between vitamin A deficiency and susceptibility to Salmonella bacteremia
uncovered an unsuspected role for NRAMP1/SLC11A1 in control of systemic S. Typhimurium infection by
neutrophils. This finding goes against the conventional wisdom that SLC11A1-dependent host defenses are
associated exclusively with macrophages. If true, this would be a novel concept and would represent a major
advance in understanding both the role of SLC11A1 and neutrophil function. The long-term goal of this proposed
work is to uncover novel mechanisms by which phagocytes control disseminated infections. We propose that a
functional difference in neutrophils expressing mutant SLC11A1, as a result of impaired bactericidal
mechanisms, increases susceptibility of SLC11A1-deficient mice to pathogens. Our central hypothesis is that
SLC11A1 function promotes the bactericidal activity of neutrophils. We will test our hypothesis using the
complementary approaches outlined in the following specific aims: (1) Define cell neutrophil-specific functions of
SLC11A1 in controlling systemic salmonellosis. (2) Determine the mechanistic basis for SLC11A1 function in
neutrophil antimicrobial activity. (3) Define how SLC11A1 promotes neutrophil-mediated disease pathology. Our
proposed work is novel and innovative in that the function of SLC11A1 in cell types other than macrophages is
not yet known. We will test our hypotheses on the role of SLC11A1 in neutrophils in a rigorous manner and with
multiple complementary lines of experimentation. This work is significant in that understanding the role of
SLC11A1 in the neutrophil will shed light on how neutrophils control disseminated Salmonella infection, and the
results are likely to open the door to studies the role of neutrophils in controlling other pathogens, such as
Leishmania and non-tuberculous mycobacteria, in which SLC11A1 function is important. It is our expectation
that the results of this work will advance our fundamental understanding of neutrophil biology as well as providing
tools and concepts to study the links between SLC11A1 and other infectious and autoimmune pathologies in
which this transporter has been implicated.

## Key facts

- **NIH application ID:** 10022095
- **Project number:** 5R01AI149632-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Renee M Tsolis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,775
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022095

## Citation

> US National Institutes of Health, RePORTER application 10022095, Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection (5R01AI149632-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022095. Licensed CC0.

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