Caspase-8 Mediates Inflammation and Disease in Rodent Malaria

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Sep 15

PMID 32929083

Citations 8

Authors

Larissa M N Pereira

Patricia A Assis

Natalia M de Araujo

Danielle F Durso

Caroline Junqueira

Marco Antonio Ataide

Dhelio B Pereira

Egil Lien

Katherine A Fitzgerald

Dario S Zamboni

Douglas T Golenbock

Ricardo T Gazzinelli

Affiliations

Soon will be listed here.

Abstract

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.

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