Multiple TLRs elicit alternative NLRP3 inflammasome activation in primary human monocytes independent of RIPK1 kinase activity.

ABSTRACT: The canonical NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway involves a priming step to induce pro-IL-1β followed by a secondary signal such as K⁺ efflux to activate inflammasome formation. This then leads to the maturation of IL-1β and the formation of gasdermin D (GSDMD) pores that initiate pyroptosis and mediate IL-1β release. In contrast, primary human monocytes also engage an alternative pathway in response to toll-like receptor (TLR) 4 activation, without the need for a secondary signal. Data from a monocyte-like cell line suggest that the alternative pathway functions via the TLR adaptor protein TIR-domain-containing adapter-inducing interferon-β (TRIF), receptor-interacting protein kinase 1 (RIPK1), FAS-associated death domain (FADD) and caspase-8 ups

SUBMITTER: Unterberger S 

PROVIDER: S-EPMC10639122 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature