Caspase-8 mediates inflammation and disease in rodent malaria.

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.

• Authors: Larissa M N Pereira, Patrícia A Assis, Natalia M de Araújo, Danielle F Durso, Caroline Junqueira, Marco Antônio Ataíde, Dhelio B Pereira, Egil Lien, Katherine A Fitzgerald, Dario S Zamboni, Douglas T Golenbock, Ricardo T Gazzinelli
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 4596 (09 14 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32929083 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Lipopolysaccharides
• Toll-Like Receptors
• Interferon-gamma
• Caspase 8
• Caspase 1

Topics

• Animals
• Brain (pathology)
• Caspase 1 (metabolism)
• Caspase 8 (metabolism)
• Dendritic Cells (metabolism)
• Enzyme Activation
• Extracellular Matrix (metabolism)
• Gene Expression Regulation
• Humans
• Inflammation (pathology)
• Interferon-gamma (metabolism)
• Interleukin-1beta (metabolism)
• Lipopolysaccharides
• Malaria, Cerebral (enzymology, genetics)
• Mice, Inbred C57BL
• Monocytes (metabolism)
• Plasmodium chabaudi (physiology)
• Spleen (metabolism)
• Toll-Like Receptors (metabolism)