Flexible Usage and Interconnectivity of Diverse Cell Death Pathways Protect against Intracellular Infection
Journal Title
Publication Type
Journal epub ahead of print
Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice and macrophages deficient for diverse combinations of caspases-1, -11, -12, and -8 and receptor interacting serine/threonine kinase 3 (RIPK3). Loss of pyroptosis, caspase-8-driven apoptosis, or necroptosis had minor impact on Salmonella control. However, combined deficiency of these cell death pathways caused loss of bacterial control in mice and their macrophages, demonstrating that host defense can employ varying components of several cell death pathways to limit intracellular infections. This flexible use of distinct cell death pathways involved extensive cross-talk between initiators and effectors of pyroptosis and apoptosis, where initiator caspases-1 and -8 also functioned as executioners when all known effectors of cell death were absent. These findings uncover a highly coordinated and flexible cell death system with in-built fail-safe processes that protect the host from intracellular infections.
Cell Press
WEHI Research Division(s)
Infectious Diseases And Immune Defence; Blood Cells And Blood Cancer; Advanced Technology And Biology; Bioinformatics; Inflammation
PubMed ID
Open Access at Publisher's Site
NHMRC Grants
Terms of Use/Rights Notice
Refer to copyright notice on published article.

Creation Date: 2020-08-05 11:11:23
Last Modified: 2020-08-05 11:49:57
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