Cargando…

Caspase-8 mediates inflammation and disease in rodent malaria

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490701/
https://www.ncbi.nlm.nih.gov/pubmed/32929083
http://dx.doi.org/10.1038/s41467-020-18295-x
Descripción
Sumario: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.