NOD Signaling and Cell Death.

Valentin J Heim,Che A Stafford,Ueli Nachbur

doi:10.3389/fcell.2019.00208

Abstract

Innate immune signaling and programmed cell death are intimately linked, and many signaling pathways can regulate and induce both, transcription of inflammatory mediators or autonomous cell death. The best-characterized examples for these dual outcomes are members of the TNF superfamily, the inflammasome receptors, and the toll-like receptors. Signaling via the intracellular peptidoglycan receptors NOD1 and NOD2, however, does not appear to follow this trend, despite involving signaling proteins, or proteins with domains that are linked to programmed cell death, such as RIP kinases, inhibitors of apoptosis (IAP) proteins or the CARD domains on NOD1/2. To better understand the connections between NOD signaling and cell death induction, we here review the latest findings on the molecular regulation of signaling downstream of the NOD receptors and explore the links between this immune signaling pathway and the regulation of cell death.

Highlights

Innate immune signaling and programmed cell death are intimately linked, and many signaling pathways can regulate and induce both, transcription of inflammatory mediators or autonomous cell death
Signaling via the intracellular peptidoglycan receptors NOD1 and NOD2, does not appear to follow this trend, despite involving signaling proteins, or proteins with domains that are linked to programmed cell death, such as RIP kinases, inhibitors of apoptosis (IAP) proteins or the caspase activation and recruitment domains (CARDs) domains on NOD1/2
pattern recognition receptors (PRR) are divided into two main groups based on their cellular localization: the transmembrane/endosome-associated PRRs, consisting of toll-like receptors (TLRs) and C-type Lectin receptors, and the cytosolic PRRs which are further divided into the RIG-1-like receptors, AIM2-like receptors and the NOD-like receptors (NLRs) (Bertin et al, 1999; Inohara et al, 1999; Ogura et al, 2001b)

Summary

NOD Signaling and Cell Death

Cell Death and Survival, a section of the journal Frontiers in Cell and Developmental. Innate immune signaling and programmed cell death are intimately linked, and many signaling pathways can regulate and induce both, transcription of inflammatory mediators or autonomous cell death. Signaling via the intracellular peptidoglycan receptors NOD1 and NOD2, does not appear to follow this trend, despite involving signaling proteins, or proteins with domains that are linked to programmed cell death, such as RIP kinases, inhibitors of apoptosis (IAP) proteins or the CARD domains on NOD1/2. To better understand the connections between NOD signaling and cell death induction, we here review the latest findings on the molecular regulation of signaling downstream of the NOD receptors and explore the links between this immune signaling pathway and the regulation of cell death

Pattern Recognition Receptors

Mechanisms of NOD Signaling

Expression of NOD Receptors

SIGNALING OUTCOMES OF NOD ACTIVATION

IS NOD SIGNALING LINKED TO CELL DEATH?

CONCLUSION AND PERSPECTIVES