NLRP3 Licenses NLRP11 for Inflammasome Activation in Human Macrophages

Overview

Journal Nat Immunol

Date 2022 May 27

PMID 35624206

Authors

Anu Gangopadhyay

Savita Devi

Shivendra Tenguria

Jessica Carriere

Huyen Nguyen

Elisabeth Jager

Hemisha Khatri

Lan H Chu

Rojo A Ratsimandresy

Andrea Dorfleutner

Christian Stehlik

Affiliations

Soon will be listed here.

Abstract

Intracellular sensing of stress and danger signals initiates inflammatory innate immune responses by triggering inflammasome assembly, caspase-1 activation and pyroptotic cell death as well as the release of interleukin 1β (IL-1β), IL-18 and danger signals. NLRP3 broadly senses infectious patterns and sterile danger signals, resulting in the tightly coordinated and regulated assembly of the NLRP3 inflammasome, but the precise mechanisms are incompletely understood. Here, we identified NLRP11 as an essential component of the NLRP3 inflammasome in human macrophages. NLRP11 interacted with NLRP3 and ASC, and deletion of NLRP11 specifically prevented NLRP3 inflammasome activation by preventing inflammasome assembly, NLRP3 and ASC polymerization, caspase-1 activation, pyroptosis and cytokine release but did not affect other inflammasomes. Restored expression of NLRP11, but not NLRP11 lacking the PYRIN domain (PYD), restored inflammasome activation. NLRP11 was also necessary for inflammasome responses driven by NLRP3 mutations that cause cryopyrin-associated periodic syndrome (CAPS). Because NLRP11 is not expressed in mice, our observations emphasize the specific complexity of inflammasome regulation in humans.

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