NOD1 and NOD2: Beyond Peptidoglycan Sensing

Overview

Journal Trends Immunol

Specialty Allergy & Immunology

Date 2017 Aug 22

PMID 28823510

Citations 80

Authors

A Marijke Keestra-Gounder

Renee M Tsolis

Affiliations

Soon will be listed here.

Abstract

NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that nucleotide-binding oligomerization domains (NODs) can also recognize a broader array of danger signals. Indeed, recent work has expanded the roles of NOD1 and NOD2 to encompass not only sensing of infections with viruses and parasites but also perceiving perturbations of cellular processes such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis. This review will comment on recent progress and point out emerging questions in these areas.

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References

Wolf A, Reyes C, Liang W, Becker C, Shimada K, Wheeler M . Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan. Cell. 2016; 166(3):624-636. PMC: 5534359. DOI: 10.1016/j.cell.2016.05.076. View

Zhou Y, Tang Y, Song Y, Li A, Zhou H, Li Y . Saturated fatty acid induces insulin resistance partially through nucleotide-binding oligomerization domain 1 signaling pathway in adipocytes. Chin Med Sci J. 2014; 28(4):211-7. DOI: 10.1016/s1001-9294(14)60004-3. View

Bhavsar A, Brown N, Stoepel J, Wiermer M, Martin D, Hsu K . The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity. PLoS Pathog. 2013; 9(7):e1003518. PMC: 3723637. DOI: 10.1371/journal.ppat.1003518. View

Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S . Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2004; 105(3):1195-7. DOI: 10.1182/blood-2004-07-2972. View

Girardin S, Boneca I, Viala J, Chamaillard M, Labigne A, Thomas G . Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003; 278(11):8869-72. DOI: 10.1074/jbc.C200651200. View

Keestra A, Winter M, Auburger J, Frassle S, Xavier M, Winter S . Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature. 2013; 496(7444):233-7. PMC: 3625479. DOI: 10.1038/nature12025. View

Ghosh R, Wang L, Wang E, Perera B, Igbaria A, Morita S . Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. 2014; 158(3):534-48. PMC: 4244221. DOI: 10.1016/j.cell.2014.07.002. View

Kufer T, Kremmer E, Adam A, Philpott D, Sansonetti P . The pattern-recognition molecule Nod1 is localized at the plasma membrane at sites of bacterial interaction. Cell Microbiol. 2007; 10(2):477-86. DOI: 10.1111/j.1462-5822.2007.01062.x. View

Vance R, Isberg R, Portnoy D . Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system. Cell Host Microbe. 2009; 6(1):10-21. PMC: 2777727. DOI: 10.1016/j.chom.2009.06.007. View

10.

Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith B, Rajendiran T, Nunez G . K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013; 38(6):1142-53. PMC: 3730833. DOI: 10.1016/j.immuni.2013.05.016. View

11.

Tanabe T, Ishige I, Suzuki Y, Aita Y, Furukawa A, Ishige Y . Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes. Biochim Biophys Acta. 2006; 1762(9):794-801. DOI: 10.1016/j.bbadis.2006.07.006. View

12.

Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J . Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem. 2003; 278(8):5509-12. DOI: 10.1074/jbc.C200673200. View

13.

Uehara A, Fujimoto Y, Kawasaki A, Kusumoto S, Fukase K, Takada H . Meso-diaminopimelic acid and meso-lanthionine, amino acids specific to bacterial peptidoglycans, activate human epithelial cells through NOD1. J Immunol. 2006; 177(3):1796-804. DOI: 10.4049/jimmunol.177.3.1796. View

14.

Zhao Y, Alonso C, Ballester I, Hye Song J, Chang S, Guleng B . Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2011; 18(4):603-12. PMC: 3594873. DOI: 10.1002/ibd.21851. View

15.

Finney C, Lu Z, Lebourhis L, Philpott D, Kain K . Disruption of Nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria. Am J Trop Med Hyg. 2009; 80(5):718-22. View

16.

Silva G, Gutierrez F, Guedes P, Horta C, Cunha L, Mineo T . Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance against Trypanosoma cruzi infection. J Immunol. 2010; 184(3):1148-52. DOI: 10.4049/jimmunol.0902254. View

17.

Kaser A, Blumberg R . ATG16L1 Crohn's disease risk stresses the endoplasmic reticulum of Paneth cells. Gut. 2013; 63(7):1038-9. PMC: 4045658. DOI: 10.1136/gutjnl-2013-306103. View

18.

Kawano Y, Akamatsu A, Hayashi K, Housen Y, Okuda J, Yao A . Activation of a Rac GTPase by the NLR family disease resistance protein Pit plays a critical role in rice innate immunity. Cell Host Microbe. 2010; 7(5):362-75. DOI: 10.1016/j.chom.2010.04.010. View

19.

Chamaillard M, Philpott D, Girardin S, Zouali H, Lesage S, Chareyre F . Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci U S A. 2003; 100(6):3455-60. PMC: 152314. DOI: 10.1073/pnas.0530276100. View

20.

McGovern D, Hysi P, Ahmad T, van Heel D, Moffatt M, Carey A . Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet. 2005; 14(10):1245-50. DOI: 10.1093/hmg/ddi135. View