# Effects of Salmonella infection on bone marrow macrophage progenitors

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $209,478

## Abstract

PROJECT SUMMARY
 Salmonella enterica serovar Typhi (S. Typhi) is a bacterial enteropathogen that causes typhoid fever, a
systemic illness that is a major problem in the developing world. Following ingestion, S. Typhi spreads from the
gut to extra-intestinal tissues, including the bone marrow (BM). The effects of Salmonella infection on BM
function are not well understood. This issue is of significance since recent studies indicate that BM
hematopoietic stem and progenitor cells (HSPCs) are reprogrammed by exposure to infection-associated
cytokines and microbial molecules and give rise to macrophages with altered properties. We have found in our
preliminary studies that the related pathogen S. Typhimurium also colonizes the BM in a mouse model of
chronic infection. Using this model, we have made the novel observation that macrophages generated from the
BM of the Salmonella-infected mice have undergone extensive changes in gene expression and
responsiveness. These alterations include significantly elevated baseline expression of numerous interferon
(IFN)-regulated genes involved in anti-viral defense, along with diminished inflammatory responses to in vitro
stimulation with lipopolysaccharide (LPS). BM-derived macrophages (BMDMs) from the Salmonella-infected
mice are also impaired in their ability to restrict pathogen growth following adoptive transfer to recipients that
are subsequently challenged with virulent S. Typhimurium. Our results suggest that chronic Salmonella
infection induces alterations in BM HSPCs that are transmitted to progeny macrophages to manifest as an
altered phenotype. The proposed studies will further characterize the mechanisms and functional significance
of these findings by (1) extending our adoptive transfer studies to analyze migration of the transferred
macrophages, as well as their effects on intestinal epithelial cells and other immune cells, and (2) comparing
the anti-viral capabilities of BMDMs from control and Salmonella-infected mice.

## Key facts

- **NIH application ID:** 10302082
- **Project number:** 1R21AI155593-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Bobby Joseph Cherayil
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,478
- **Award type:** 1
- **Project period:** 2021-05-14 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302082

## Citation

> US National Institutes of Health, RePORTER application 10302082, Effects of Salmonella infection on bone marrow macrophage progenitors (1R21AI155593-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10302082. Licensed CC0.

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