# Study of the Cell-specific Inflammasome Responses During Defense Against Gram-negative Bacteria

> **NIH NIH P20** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $250,791

## Abstract

Project Summary/Abstract 
  
Resident macrophages are often the first cells to detect bacterial contamination of a tissue, and use 
inflammatory caspases such as caspases-1 and -11 to distinguish virulent from avirulent bacteria. When 
activated by sensors that detect pathological bacterial activity, caspase-1 processes pro-IL-1β and pro-IL- 
18 to their mature and secreted forms to recruit additional immune cells. In addition, caspase-1 also 
triggers a lytic form of programmed cell death called pyroptosis. In contrast, caspase-11 induces 
pyroptosis, but cannot process pro-IL-1β or IL-18 alone. 
Neutrophils are a major cell type recruited to early sites of infection. However, whether neutrophils also 
express inflammatory caspases in order to detect bacterial virulence remains unclear. Intriguingly, 
neutrophils express numerous pattern recognition receptors and sensors upstream of caspases, but their 
function in infection has not been thoroughly studied. 
Given the importance of inflammasomes in macrophages, and the importance of neutrophils in 
sterilizing infection, it is likely that neutrophils also use inflammasomes to tune their responses to infection. 
Indeed, we found that neutrophil caspase-11 is activated and clears infected neutrophils with extreme 
efficiency. Thus, in this grant, we propose to compare and contrast the inflammasome signaling pathways 
in neutrophils and macrophages, and determine the role of inflammasome in each cellular compartment 
during defense against intracellular and extracellular infection. Determining the role of inflammasomes in 
neutrophils may provide new perspectives about the function of neutrophils during infection, as well as 
insight into potentially novel and innovative therapeutic strategies aimed at preventing cytosolic infection in 
neutrophils.

## Key facts

- **NIH application ID:** 10161251
- **Project number:** 5P20GM103625-09
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Youssef Aachoui
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $250,791
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161251

## Citation

> US National Institutes of Health, RePORTER application 10161251, Study of the Cell-specific Inflammasome Responses During Defense Against Gram-negative Bacteria (5P20GM103625-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10161251. Licensed CC0.

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