# Role of inflammatory monocytes in Salmonella-induced colitis

> **NIH NIH R21** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $196,012

## Abstract

PROJECT SUMMARY
Salmonella enterica serovars are pathogenic bacteria that cause significant morbidity and mortality in humans
worldwide. Gastroenteritis is the most prevalent of the clinical syndromes associated with Salmonella enterica
serovars and is caused by nontyphoidal Salmonella enterica serovars such as Salmonella enterica serovar
Typhimurium (STm) in immunocompetent individuals. As part of our ongoing studies aimed at elucidating
mechanisms by which STm establish infection and avoid immune clearance, we began to investigate the role
of inflammatory monocytes (IM, CD11b+ Ly6Chi Ly6G- cells) in STm-induced colitis. IM are innate immune cells
that play a key role in immunity and host defense. IM originate from progenitors in bone marrow (BM) and,
under certain pathological conditions, can be recruited from BM into peripheral tissues. We previously
published that IM purified from tissues of mice infected with STm exhibit both protective and
immunosuppressive properties that may influence the outcome of the infection. Furthermore, we recently
published that IM provide a niche for STm expansion in the lumen of the inflamed intestine. These published
findings from our laboratory established that IM play a key role in the pathogenesis of STm-induced colitis.
Most recently, we have found that IM purified from ceca of mice infected with STm produce tumor necrosis
factor (TNF)-α, a cytokine that mediates the early pathology in STm infection of the gastrointestinal tract; and
express the receptor for interferon (IFN)-γ, a cytokine that delays resolution of STm-induced intestinal
inflammation. The objective of this application is to define how IM contribute to the pathogenesis of STm-
induced colitis, a high impact topic important for understanding the role of IM in immunity and host defense.
Our central hypothesis is that IM contribute both directly and indirectly to the pathogenesis of STm-induced
colitis. To test different aspects of our central hypothesis and accomplish our objective, we will 1) identify the
cecal cell type(s) that produce the monocyte chemoattractant CCL2 during STm infection and determine
whether Ccl2 expression by myeloid cells is required for the accumulation of IM in ceca of mice infected with
STm, 2) define how IM are exploited to promote STm expansion in the lumen of the inflamed intestine, and 3)
determine whether Tnfa or Ifngr1 expression by IM contributes to the severity of the pathology of STm-induced
colitis. Conceptual advances resulting from the proposed research are expected to provide new, fundamental
insights into host interactions with bacterial pathogens and thus will have a strong and sustained influence on
the field.

## Key facts

- **NIH application ID:** 10214501
- **Project number:** 5R21AI153675-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Adrianus Wilhelmus Maria van der Velden
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,012
- **Award type:** 5
- **Project period:** 2020-07-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214501

## Citation

> US National Institutes of Health, RePORTER application 10214501, Role of inflammatory monocytes in Salmonella-induced colitis (5R21AI153675-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214501. Licensed CC0.

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