A Dectin-1-Caspase-8 Pathway Licenses Canonical Caspase-1 Inflammasome Activation and Interleukin-1β Release in Response to a Pathogenic Fungus.

ABSTRACT:

Background

Paracoccidioides brasiliensis is equipped with an arsenal of virulence factors that are crucial for causing infection. Our group previously defined the NLRP3 inflammasome as a mediator of P brasiliensis-induced cell damage recognition and induction of effective Th1 immune responses. However, deficiency of caspase-1 only partially reduced interleukin (IL)-1β levels.

Methods

In this study, using chemical inhibitors as well as genetically modified mice, we identify an additional pathway for IL-1β production in response to P brasiliensis infection.

Results

Paracoccidioides brasiliensis initiated caspase-8-mediated IL-1β production, an event that was necessary for transcriptional priming and posttranslational processing of pro-IL-1β. Caspase-8 synergizes with th

SUBMITTER: Ketelut-Carneiro N 

PROVIDER: S-EPMC6279136 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature