UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2020-09-14

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Hemic and Immune Systems | Immunology of Infectious Disease | Immunopathology | Parasitic Diseases | Parasitology

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 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.

Keywords

Infectious diseases, Inflammation, Parasite host response, Malaria

Rights and Permissions

Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-020-18295-x

Source

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

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID

32929083

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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