Department of Medicine, Division of Infectious Diseases and Immunology
Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Hemic and Immune Systems | Immunology of Infectious Disease | Immunopathology | Parasitic Diseases | Parasitology
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 TNFalpha and IL-1beta 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.
Infectious diseases, Inflammation, Parasite host response, Malaria
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DOI of Published Version
Pereira LMN, Assis PA, de Araújo NM, Durso DF, Junqueira C, Ataíde MA, Pereira DB, Lien E, Fitzgerald KA, Zamboni DS, Golenbock DT, Gazzinelli RT. Caspase-8 mediates inflammation and disease in rodent malaria. Nat Commun. 2020 Sep 14;11(1):4596. doi: 10.1038/s41467-020-18295-x. PMID: 32929083; PMCID: PMC7490701. Link to article on publisher's site
Pereira LM, Assis PA, de Araujo NM, Fernandes Durso D, Junqueira C, Ataide MA, Pereira DB, Lien E, Fitzgerald KA, Zamboni DS, Golenbock DT, Gazzinelli RT. (2020). Caspase-8 mediates inflammation and disease in rodent malaria. Open Access Articles. https://doi.org/10.1038/s41467-020-18295-x. Retrieved from https://escholarship.umassmed.edu/oapubs/4372
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