A long-awaited merger of the pathways mediating host defence and programmed cell death

Nat Rev Immunol. 2014 Sep;14(9):601-18. doi: 10.1038/nri3720.

Abstract

Historically, cell death and inflammation have been closely linked, but the necessary divergence of the fields in the past few decades has enriched our molecular understanding of the signalling pathways that mediate various programmes of cell death and multiple types of inflammatory responses. The fields have now come together again demonstrating a surprising level of integration. Intimate interconnections at multiple levels are revealed between the cell death and inflammatory signal transduction pathways that are mobilized in response to the engagement of pattern recognition receptors during microbial infection. Molecules such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, FAS-associated death domain protein (FADD), FLICE-like inhibitory protein (FLIP) and caspase 8 - which are associated with different forms of cell death - are incorporated into compatible and exceedingly dynamic Toll-like receptor, NOD-like receptor and RIG-I-like receptor signalling modules. These signalling modules have a high capacity to switch from inflammation to cell death, or a programmed execution of both, all in an orchestrated battle for host defence and survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology
  • Animals
  • Apoptosis / immunology*
  • Autophagy / immunology*
  • Carrier Proteins / immunology
  • Caspases / genetics
  • Caspases / immunology
  • Fas-Associated Death Domain Protein / immunology
  • Gram-Negative Bacteria / immunology
  • Gram-Negative Bacterial Infections / immunology
  • Humans
  • Inflammation*
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptor-Interacting Protein Serine-Threonine Kinases / immunology
  • Signal Transduction / immunology
  • Toll-Like Receptors / immunology

Substances

  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Fas-Associated Death Domain Protein
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • TICAM1 protein, human
  • Toll-Like Receptors
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Caspases