IAPs regulate distinct innate immune pathways to co-ordinate the response to bacterial peptidoglycans
- Author(s)
- Stafford, CA; Lawlor, KE; Heim, VJ; Bankovacki, A; Bernardini, JP; Silke, J; Nachbur, U;
- Details
- Publication Year 2018-02-06,Volume 22,Issue #6,Page 1496-1508
- Journal Title
- Cell Rep
- Publication Type
- Journal Article
- Abstract
- Inhibitors of apoptosis (IAPs) proteins are critical regulators of innate immune signaling pathways and therefore have potential as drug targets. X-linked IAP (XIAP) and cellular IAP1 and IAP2 (cIAP1 and cIAP2) are E3 ligases that have been shown to be required for signaling downstream of NOD2, an intracellular receptor for bacterial peptidoglycan. We used genetic and biochemical approaches to compare the responses of IAP-deficient mice and cells to NOD2 stimulation. In all cell types tested, XIAP is the only IAP required for signaling immediately downstream of NOD2, while cIAP1 and cIAP2 are dispensable for NOD2-induced nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) activation. However, mice lacking cIAP1 or TNFR1 have a blunted cytokine response to NOD2 stimulation. We conclude that cIAPs regulate NOD2-dependent autocrine TNF signaling in vivo and highlight the importance of physiological context in the interplay of innate immune signaling pathways.
- Publisher
- Cell Press
- Keywords
- IAPs; Nod2; Ripk2; cell signaling; inflammation; innate immunity
- Research Division(s)
- Cell Signalling And Cell Death; Inflammation
- PubMed ID
- 29425505
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2018.01.024
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2018.01.024- NHMRC Grants
- NHMRC/1046986, NHMRC/1057888, NHMRC/541901, NHMRC/1058190,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-02-28 08:05:03
Last Modified: 2018-02-28 08:50:43