# Host-derived extracellular vesicles in inflammatory caspase activation

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $410,000

## Abstract

Inflammasome related caspases such as caspase-1, caspase-4, and caspase-11 are a subset of
the caspase family specialized in executing a lytic form of cell death and IL-1 cytokine-based
inflammatory response. The activation of these inflammatory caspases is strongly coupled to
innate immune detection of infections and cellular perturbations via canonical and noncanonical
inflammasomes. Inflammasomes are multiprotein complexes in the cytosol assembled in
response to wide variety of pathogen-associated molecular patterns (PAMPs) including nucleic
acids, toxins, flagellin, and cell wall components and endogenous danger signals (danger-
associated molecular patterns, or DAMPs) such as ATP and uric acid crystals. The assembly of
inflammasome complex leads to the autoproteolytic activation of inflammatory caspases.
Enzymatically active versions of inflammatory caspases activate a pore forming protein called
gasdermin D, which lyses the cells via plasma membrane perforation. Active caspase-1 also
cleaves the inflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms. Inflammatory
caspases are important for initiating the inflammatory response against a wide variety of
pathogens including bacteria and viruses. Inflammatory caspases also play crucial roles in sepsis,
a major life-threatening condition associated with infections. Extracellular vesicles (EVs) are
membrane-bound structures abundantly released by our living cells into the extracellular space.
EVs are packaged with proteins, lipids, and RNAs, and EVs have emerged as a crucial mode of
inter-cellular transfer of all three cargoes. EV-cargoes are functional and modulate the physiology
of the recipient cells. However, the role of EVs in the inflammasome signaling is poorly
understood. This proposal seeks to comprehensively address this critical knowledge gap in three
specific aims. Aim 1 will characterize the impact of host-derived EVs on inflammatory caspase
activation by PAMPs. Aims 2 and 3 will demonstrate the molecular and cellular mechanisms by
which the host-derived EVs regulate PAMP-activation of inflammatory caspases. In summary, this
proposal will reveal a new role for host-derived EVs in inflammasome responses in the context of
host defense with great implications for human infectious diseases and sepsis.

## Key facts

- **NIH application ID:** 9973550
- **Project number:** 1R01AI148491-01A1
- **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:** 2020
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2020-01-16 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973550

## Citation

> US National Institutes of Health, RePORTER application 9973550, Host-derived extracellular vesicles in inflammatory caspase activation (1R01AI148491-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973550. Licensed CC0.

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