# Cytosolic Immune Surveillance During Bacterial Infections

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $410,000

## Abstract

Inflammasomes sense an array of pathogen-associated molecular patterns (PAMPs) and
damage-associated molecular patterns (DAMPs) generated during infection and trauma and
represent the first line of defense against infections. In the canonical form, inflammasomes consist
of a sensor protein that recognizes PAMPs, an adaptor molecule ASC, and an effector protease,
caspase-1. In the noncanonical form, inflammatory caspases related to caspase-1, namely
caspase-11 and caspase-4, directly sense cytosolic lipopolysaccharide (LPS) from Gram-
negative bacteria and their outer membrane vesicle. Inflammasome signaling culminates in the
post-translational activation of IL-1β, IL-18, gasdermin D (a pore-forming protein), and pyroptosis,
a lytic and inflammatory form of cell death, and the simultaneous release of DAMPs. Despite the
profound implications of inflammasome responses in infections, cancer, and autoimmunity, the
regulatory modules that fine-tune the initiation and termination of inflammasome signaling remain
mostly unknown. This proposal seeks to comprehensively address this critical knowledge gap in
three specific aims by focusing on galectins, a family of β-galactoside-binding proteins. Owing to
their capacity to bind to N- or O-glycan termini of various glycoproteins and regulate their
membrane localization and signal transduction, galectins have diverse functions in various
physiological and pathological processes. Aims 1 and 2 of the proposal will investigate galectins'
role in noncanonical inflammasome signaling in murine and human cells and in vivo. Aim 3 will
explore how galectins control canonical inflammasome signaling in vitro and in vivo. In summary,
the findings from this project would reveal new players in inflammasome signaling with significant
implications for human infectious diseases and sepsis.

## Key facts

- **NIH application ID:** 10416062
- **Project number:** 5R01AI119015-07
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Vijay Rathinam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,000
- **Award type:** 5
- **Project period:** 2016-03-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416062

## Citation

> US National Institutes of Health, RePORTER application 10416062, Cytosolic Immune Surveillance During Bacterial Infections (5R01AI119015-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10416062. Licensed CC0.

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