# Bacterial modulation of noncanonical inflammasome

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $398,750

## Abstract

Project Summary/Abstract
 The innate immune system employs germline-encoded pattern recognition receptors to
survey the extra- and intra-cellular milieu for the presence of invading microbial or danger
signals and mount appropriate defense responses. Inflammasomes, the multiprotein complexes
assembled in the cytosol in response to microbial and endogenous danger signals, have
emerged as a central component of the innate immune surveillance system. Once assembled
inflammasomes proteolytically activate caspase-1, which in turn induces cell death and
production of IL-1β and IL-18. Most recently a noncanonical NLRP3 inflammasome pathway
was identified that is activated by LPS that enters the cytosol via outer membrane vesicles
during infection with Gram-negative bacteria such as Enterohemorrhagic E. coli (EHEC).
Cytosolic LPS binds and activates an inflammatory caspase, caspae-11, which then mediates
cell death, caspase-1 activation and downstream IL-1 cytokine production. Inflammasomes,
including the caspase-11-mediated noncanonical inflammasome, play a crucial role in the
clearance of infectious agents via pyroptotic and IL-1 responses. A strong selection pressure
from the host such as this drives pathogens to develop strategies to actively antagonize or
evade innate immune responses. However, little is known about regulation of caspase-11-
mediated noncanonical inflammasome by bacterial pathogens. This project will address
this knowledge gap and will focus on examining the modulation of noncanonical inflammasome
by bacteria utilizing EHEC as a model organism. The studies proposed in the three specific
aims of this project will systematically characterize how two bacterial virulence factors inhibit the
noncanonical inflammasome and determine the underlying mechanisms. Identifying the
mechanisms by which pathogenic bacteria silence noncanonical inflammasome is crucial as it
may aid in designing novel therapeutic approaches against Gram-negative infections.

## Key facts

- **NIH application ID:** 10077533
- **Project number:** 5R01AI132850-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Sivapriya Kailasan Vanaja
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $398,750
- **Award type:** 5
- **Project period:** 2018-01-16 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077533

## Citation

> US National Institutes of Health, RePORTER application 10077533, Bacterial modulation of noncanonical inflammasome (5R01AI132850-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077533. Licensed CC0.

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