| First Author | Pereira LMN | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 4596 |
| PubMed ID | 32929083 | Mgi Jnum | J:296533 |
| Mgi Id | MGI:6467908 | Doi | 10.1038/s41467-020-18295-x |
| Citation | Pereira LMN, et al. (2020) Caspase-8 mediates inflammation and disease in rodent malaria. Nat Commun 11(1):4596 |
| abstractText | 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. |
