Caspase-8 mediates inflammation and disease in rodent malaria

Author(s):Show less -

Pereira, Larissa M. N. ^{[1, 2, 3]} ; Assis, Patricia A. ^[3] ; de Araujo, Natalia M. ^{[1, 2]} ; Durso, Danielle F. ^[3] ; Junqueira, Caroline ^[2] ; Ataide, Marco Antonio ^{[1, 2]} ; Pereira, Dhelio B. ^[4] ; Lien, Egil ^[3] ; Fitzgerald, Katherine A. ^[3] ; Zamboni, Dario S. ^[5] ; Golenbock, Douglas T. ^{[2, 3]} ; Gazzinelli, Ricardo T. ^{[1, 2, 3, 6]}

Affiliation

^[1] Univ Fed Minas Gerais, Dept Bioquim & Imunol, ICB, BR-31270901 Belo Horizonte, MG - Brazil

^[2] FIOCRUZ MG, Inst Rene Rachou, BR-30190002 Belo Horizonte, MG - Brazil

^[3] Univ Massachusetts, Dept Med, Med Sch, Worcester, MA 01605 - USA

^[4] FIOCRUZ RO, Ctr Pesquisas Med Trop, BR-76812329 Porto Velho, RO - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Fundacao Oswaldo Cruz, Fac Med Ribeirao Preto, Plataforma Med Translac, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 11, n. 1 SEP 14 2020.
• Web of Science Citations: 3

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 TNF alpha and IL-1 beta 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. (AU)

• FAPESP's process: 16/23618-8 - Immunological mechanisms of resistance and disease in malaria
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants