# Role of NRAMP1/SLC11A1 in Salmonella pathogenesis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $196,250

## Abstract

ABSTRACT
 This exploratory/developmental application proposes to interrogate how the divalent cation transporter
NRAMP1/SLC11A1 mediates control of Salmonella infection. 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 definitive
experiment to test this idea would be infection of mice that are conditionally deficient for SLC11A1 only in
neutrophils. However, given the reliance of the field on C57BL/6 mouse strains, that express a defective Slc11a1
allele, tools and constructs for generating conditionally defective mice currently do not exist. We propose to fill
this gap by generating and utilizing mice carrying a “floxed” Slc11a1 allele to study cell type-specific roles of
SLC11A1 in immunity to bacterial infection. The premise for our proposed approach is strong, as (i) SLC11A1 is
critical to controlling intracellular pathogens; (ii) SLC11A1 has been implicated in human autoimmune diseases
involving neutrophil function and (iii) we present clear preliminary results supporting a role for SLC11A1 in
neutrophil function in vitro. My lab group has enlisted the support of the UC Davis Mouse Biology Program, which
is one of the leads in the Knockout Mouse Project (KOMP) consortium and has successfully produced over 950
knockout mouse lines. Further, we have a set of tools and assays established in our lab to successfully complete
the proposed studies. 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 hypothesis that SLC11A1 plays a role in neutrophil
antimicrobial response 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 on 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 is that the results of this work will advance our fundamental
understanding of neutrophil biology as well as providing tools to study the links between SLC11A1 and other
infectious and autoimmune pathologies, in which this transporter has been implicated.

## Key facts

- **NIH application ID:** 9832686
- **Project number:** 5R21AI143253-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Renee M Tsolis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2018-12-07 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832686

## Citation

> US National Institutes of Health, RePORTER application 9832686, Role of NRAMP1/SLC11A1 in Salmonella pathogenesis (5R21AI143253-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832686. Licensed CC0.

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