Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.

Journal Article (Journal Article;Review)

Innate immune sensors can recognize when host cells are irrevocably compromised by pathogens, and in response can trigger programmed cell death (pyroptosis, apoptosis, and necroptosis). Innate sensors can directly bind microbial ligands; for example, NAIP/NLRC4 detects flagellin/rod/needle, whereas caspase-11 detects lipopolysaccharide. Other sensors are guards that monitor normal function of cellular proteins; for instance, pyrin monitors Rho GTPases, whereas caspase-8 and receptor-interacting protein kinase (RIPK)3 guards RIPK1 transcriptional signaling. Some proteins that need to be guarded can be duplicated as decoy domains, as seen in the integrated decoy domains within NLRP1 that watch for microbial attack. Here, we discuss the evolutionary battle between pathogens and host innate immune sensors/guards, illustrated by the Red Queen hypothesis. We discuss in depth four pathogens, and how they either fail in this evolutionary race (Chromobacterium violaceum, Burkholderia thailandensis), or how the evolutionary race generates increasingly complex virulence factors and host innate immune signaling pathways (Yersinia species, and enteropathogenic Escherichia coli [EPEC]).

Full Text

Duke Authors

Cited Authors

  • Lacey, CA; Miao, EA

Published Date

  • February 3, 2020

Published In

Volume / Issue

  • 12 / 2

PubMed ID

  • 31501197

Pubmed Central ID

  • PMC6996452

Electronic International Standard Serial Number (EISSN)

  • 1943-0264

Digital Object Identifier (DOI)

  • 10.1101/cshperspect.a036459


  • eng

Conference Location

  • United States