# Innate responses following infection with enteric microbes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $348,750

## Abstract

Globally, 4-6 million people die of enteric infections each year. Even within the United States, Salmonella
and other gastroenteric infections are responsible for millions of illness, thousands of deaths and billion-dollar
of expenditure from food recall and hospital associated expenses. The innate immune system is the first line
of defense against pathogens. After entering intestinal epithelial cells, enteric microbes encounter phagocytes
and generate inflammation. However, our understanding about how phagocytes interact, clear, and generate
inflammation only from the enteric pathogen is incomplete. Endosomal systems connect innate to adaptive
immunity by degrading the pathogenic microbe and presenting the antigens but our knowledge is limited to
their responses to immune signaling.
 Bacterial recognition by host cells is fundamental for the initiation of mucosal immune responses during the
infection process. As a consequence of this interaction, signaling cascades are activated in host cells that lead
to inflammatory responses and/or phagocytic clearance of attached bacteria. Previously, we found that BAI1
(Brain Angiogenesis Inhibitor 1) recognizes bacterial lipopolysaccharide (LPS) in a unique mechanism than the
well-known Toll like receptor 4 (TLR4). BAI1 binds ELMO1 (EnguLfment and cell Motility protein 1) that
facilitates the engulfment of bacteria and induces inflammatory responses. While both pathogenic and
commensal-Gram-negative bacteria express lipopolysaccharide (LPS), intestinal phagocytes are able to
discriminate commensals from enteric pathogens. Preliminary results show that interactions between bacterial
effector molecules and ELMO1 modulate TNF-α production. My general hypothesis is that the sensing of
enteric microbes by ELMO1 conduits signaling events that regulate host immune responses.
 The broad objectives for the proposed studies are to understand the microbial sensing by the host
engulfment pathway that generates differential innate responses in the mucosa and the pathogenesis of
enteric infections. These objectives will be addressed in the following Specific Aims:
Aim 1: Define the role of the engulfment pathway in host inflammatory responses.
Aim 2: Determine the bacterial effectors that regulate the engulfment pathway.
Aim 3: Define the role of bacterial effector interactions in innate immunity.
 The proposed studies will delineate the molecular basis whereby a host signaling pathway uptakes enteric
pathogens, associates with endosomal signaling and regulates immune responses. As such, they will provide
new mechanism involving bacterial effectors in regulating intestinal innate responses that are relevant to
Salmonella and other enteric infections. A more complete knowledge of these aspects of microbial interaction
with innate immune system will lead to targeted therapies for antimicrobial resistant infections and broadly to
limit inflammation-linked diseases.

## Key facts

- **NIH application ID:** 10003264
- **Project number:** 5R01DK107585-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Soumita Das
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003264

## Citation

> US National Institutes of Health, RePORTER application 10003264, Innate responses following infection with enteric microbes (5R01DK107585-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003264. Licensed CC0.

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