# Microbial Pattern Recognition and Signaling by the Adhesion GPCR BAI1

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $517,076

## Abstract

Abstract
 The innate immune system forms the first line of specific host defense against invading microbial
pathogens. Integral to the innate immune response are Pattern Recognition Receptors (PRRs), which
recognize conserved determinants expressed by a broad range of pathogenic microorganisms. Among these
are the Toll-like receptors, which promote inflammatory signaling and phagocyte recruitment in response to
pathogen recognition, and several families of phagocytic PRRs that mediate phagocytic clearance of microbes
from infected tissues. Each receptor family contains multiple members that recognize a unique spectrum of
microbial components, and collectively they provide protection against a wide range of infectious organisms.
 We have identified a novel pattern recognition receptor, BAI1, that specifically recognizes the surface
lipopolysaccharide (LPS) of Gram-negative bacteria. BAI1 is a member of a poorly understood family of G-
protein coupled receptors (GPCRs), the so-called Adhesion GPCRs. Binding of bacteria to BAI1 triggers their
rapid internalization and killing by host phagocytes, through a mechanism involving activation of the small
GTPase Rac by the Elmo/Dock GEF complex, which interacts directly with BAI1. Whether and how signaling
through heterotrimeric G proteins is integrated into this process is not known, and will be the focus of Aim 1.
 An emerging theme in innate immunity is that pattern recognition receptors often cooperate with each
other to enhance downstream signaling responses. Our published and preliminary data indicate that BAI1 acts
in tandem with the Toll-like receptor TLR4 to promote the production of reactive oxygen species (ROS) by
phagocytic cells, and the synthesis of a subset of inflammatory cytokines/chemokines/interferons whose
expression is mediated by the transcription factor IRF3. In Aim 2 we will determine how signals derived from
BAI1 influence TLR4-mediated signaling to drive ROS production and the transcription of pro-inflammatory
genes.
 The ultimate goal of the proposed research is to define the role of BAI1 in host defense against
bacterial infection. In Aim 3, we will characterize the ability of BAI1-deficient macrophages and neutrophils to
clear infection in a mouse model of Gram-negative peritonitis. The ability of BAI1 to drive ROS production and
cytokine/interferon synthesis in specific myeloid cell subsets during infection will also be determined. Together
these studies will provide unique biochemical and physiological insights into a new class of pattern recognition
receptor with important functions in the innate immune response to bacterial pathogens. Moreover, BAI1 is one
of the few Adhesion GPCRs with known physiological ligands, and dissection of its signaling properties will
reveal new insights into this poorly understood class of receptors.

## Key facts

- **NIH application ID:** 10292453
- **Project number:** 5R01AI136073-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** James E. Casanova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $517,076
- **Award type:** 5
- **Project period:** 2017-11-17 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292453

## Citation

> US National Institutes of Health, RePORTER application 10292453, Microbial Pattern Recognition and Signaling by the Adhesion GPCR BAI1 (5R01AI136073-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10292453. Licensed CC0.

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