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- Title
Caspase-8 mediates inflammation and disease in rodent malaria.
- Authors
Pereira, Larissa M. N.; Assis, Patrícia A.; de Araújo, Natalia M.; Durso, Danielle F.; Junqueira, Caroline; Ataíde, Marco Antônio; Pereira, Dhelio B.; Lien, Egil; Fitzgerald, Katherine A.; Zamboni, Dario S.; Golenbock, Douglas T.; Gazzinelli, Ricardo T.
- 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. Inflammasome activation plays a role in malaria pathogenesis, but details aren't well understood. Here, the authors show that caspase-8 is a central mediator of systemic inflammation in rodent malaria and that monocytes from malaria patients express active caspases-1, -4 and -8.
- Subjects
CEREBRAL malaria; INFLAMMATORY mediators; PATHOLOGY; SEPTIC shock; RODENTS; MALARIA
- Publication
Nature Communications, 2020, Vol 11, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-18295-x