Domínguez-Martínez DA, Núñez-Avellaneda D, Castañón-Sánchez CA, Salazar MI

Language: English
References: 59
Page: 18-28
PDF size: 628.31 Kb.

ABSTRACT

Nucleotide-binding domain (NBD) leucine-rich repeat (LRR)-containing receptors or NLRs are a family of receptors that detect both, molecules associated to pathogens and alarmins, and are located mainly in the cytoplasm. NOD2 belongs to the NLR family and is a dynamic receptor capable of interacting with multiple proteins and modulate immune responses in a stimuli-dependent manner. The experimental evidence shows that interaction between NOD2 structural domains and the effector proteins shape the overall response against bacterial or viral infections. Other reports have focused on the importance of NOD2 not only in infection but also in maintaining tissue homeostasis. However, not only protein interactions relate to function but also certain polymorphisms in the gene that encodes NOD2 have been associated with inflammatory diseases, such as Crohn’s disease. Here, we review the importance and general characteristics of NOD2, discussing its participation in infections caused by bacteria and viruses as well as its interaction with other pathogen recognition receptors or effectors to induce antibacterial and antiviral responses. Finally, the role of NOD2 in chronic inflammatory conditions and its potential to be targeted therapeutically are examined.

REFERENCES

1. Shaw MH, Reimer T, Kim YG, Nuñez G. NOD-like receptors (NLRs): Bona fide intracellular microbial sensors. Curr Opin Immunol. 2008;20:377-82.

2. Krishnaswamy JK, Chu T, Eisenbarth SC. Beyond pattern recognition: NOD-like receptors in dendritic cells. Trends Immunol. 2013;34:224-33.

3. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140:805-20.

4. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499-511.

5. Wu J, Chen ZJ. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol. 2014;32:461-88.

6. Yoneyama M, Kikuchi M, Matsumoto K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005;175:2851-8.

7. Kolakofsky D, Kowalinski E, Cusack S. A structure-based model of RIG-I activation. RNA. 2012;18:2118-27.

8. Kanneganti T. Central roles of NLRs and inflammasomes in viral infection. Nat Rev Immunol. 2010;10:688-98.

9. Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13:397-411.

10. Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660-5.

11. Ting J, Duncan J, Lei Y. How the noninflammasome NLRs function in the innate immune system. Science. 2010;327: 286-90.

12. Byrne BG, Dubuisson JF, Joshi AD, Persson JJ, Swanson MS. Inflammasome components coordinate autophagy and pyroptosis as macrophage responses to infection. MBio. 2013;4: e00620-12.

13. Lamkanfi M, Kanneganti TD. Regulation of immune pathways by the NOD-like receptor NLRC5. Immunobiology. 2012; 217:13-6.

14. Lupfer C, Kanneganti T. Unsolved mysteries in NLR biology. Front Immunol. 2013;4:285.

15. Keestra-Gounder AM, Byndloss MX, Seyffert N, et al. NOD1 and NOD2 signalling links ER stress with inflammation. Nature. 2016;532:394-7.

16. Strober W, Watanabe T. NOD2, an intracellular innate immune sensor involved in host defense and crohn’s disease. Mucosal Immunol. 2011;4:484-95.

17. Lécine P, Esmiol S, Métais JY, et al. The NOD2-RICK complex signals from the plasma membrane. J Biol Chem 2007;282: 15197-207.

18. Fritz JH, Girardin SE, Fitting C, et al. Synergistic stimulation of human monocytes and dendritic cells by toll-like receptor 4 and NOD1-and NOD2-activating agonists. Eur J Immunol. 2005;35:2459-70.

19. Travassos LH, Girardin SE, Philpott DJ, et al. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Rep. 2004;5:1000-6.

20. Leber JH, Crimmins GT, Raghavan S, et al. Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog. 2008;4:e6.

21. Landes MB, Rajaram MV, Nguyen H, Schlesinger LS. Role for NOD2 in Mycobacterium tuberculosis-induced iNOS expression and no production in human macrophages. J Leukoc Biol. 2015;97:1111-9.

22. Wang H, Yu G, Yu H, et al. Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model. Acta Vet Scand. 2015;57:25.

23. Liu X, Han Q, Leng J. Analysis of nucleotide-binding domain oligomerization domain proteins in a murine model of pneumococcal meningitis. BMC Infect Dis. 2014;14:648.

24. Marchesan J, Jiao Y, Schaff RA, et al. TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens. Mol Oral Microbiol. 2016;31:243-58.

25. Prates TP, Taira TM, Holanda MC, et al. NOD2 contributes to Porphyromonas gingivalis-induced bone resorption. J Dent Res 2014;93:1155-62.

26. Lecat A, Piette J, Legrand-Poels S. The protein nod2: An innate receptor more complex than previously assumed. Biochem Pharmacol. 2010;80:2021-31.

27. Hasegawa M, Fujimoto Y, Lucas PC, et al. A critical role of RICK/ RIP2 polyubiquitination in nod-induced NF-kappaB activation. EMBO J. 2008;27:373-83.

28. Jakopin Ž. Nucleotide-binding oligomerization domain (NOD) inhibitors: A rational approach toward inhibition of NOD signaling pathway. J Med Chem. 2014;57:6897-918.

29. Wertz IE, Dixit VM. Signaling to NF-kappaB: Regulation by ubiquitination. Cold Spring Harb Perspect Biol. 2010;2: a003350.

30. Hsu YM, Zhang Y, You Y, et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol. 2007;8:198-205.

31. Travassos LH, Carneiro LA, Ramjeet M, et al. Nod1 and nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol. 2010; 11:55-62.

32. Anand PK, Tait SW, Lamkanfi M, et al. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J Biol Chem. 2011;286:42981-91.

33. Cooney R, Baker J, Brain O, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2010;16:90-7.

34. Monie TP. NLR activation takes a direct route. Trends Biochem Sci. 2013;38:131-9.

35. Coutermarsh-Ott S, Eden K, Allen IC. Beyond the inflammasome: Regulatory NOD-like receptor modulation of the host immune response following virus exposure. J Gen Virol. 2016; 97:825-38.

36. Sabbah A, Chang TH, Harnack R, et al. Activation of innate immune antiviral responses by nod2. Nat Immunol. 2009;10:1073-80.

37. Vissers M, Remijn T, Oosting M, et al. Respiratory syncytial virus infection augments NOD2 signaling in an IFN-β-dependent manner in human primary cells. Eur J Immunol. 2012;42: 2727-35.

38. Hernandez J, Giraldo D, Paul S, Urcuqui-Inchima S. Involvement of neutrophil hyporesponse and the role of toll-like receptors in human immunodeficiency virus 1 protection. PLoS One. 2015;10:e0119844.

39. Le Bel M, Gosselin J. Leukotriene B4 enhances NOD2-dependent innate response against influenza virus infection. PLoS One. 2015;10:e0139856.

40. Lei Q, Li L, Cai J, et al. ORF3 of hepatitis E virus inhibits the expression of proinflammatory cytokines and chemotactic factors in LPS-stimulated human PMA-THP1 cells by inhibiting NF-κB pathway. Viral Immunol. 2016;29:105-11.

41. Lupfer C, Thomas P, Anand P, et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol. 2013;14:480-8.

42. Lupfer C, Thomas P, Kanneganti T. Nucleotide oligomerization and binding domain 2-dependent dendritic cell activation is necessary for innate immunity and optimal CD8+ T Cell responses to influenza a virus infection. J Virol. 2014;88:8946-55.

43. Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731-4.

44. Moreira LO, Zamboni DS. NOD1 and NOD2 signaling in infection and inflammation. Front Immunol. 2012;3:328.

45. Jaskula E, Lange A, Kyrcz-Krzemien S, Markiewicz M, Dzierzak-Mietla M, Jedrzejczak WW, et al. NOD2/CARD15 single nucleotide polymorphism 13 (3020insC) is associated with risk of sepsis and single nucleotide polymorphism 8 (2104C>T) with herpes viruses reactivation in patients after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:409-14.

46. Tello-Ruiz M, Walsh E, Rioux J. Gastroenterologic and hepatic disease. Madame Curie Bioscience Database. Austin (TX): Lande Bioscience; 2000.

47. Cantó E, Ricart E, Busquets D, et al. Influence of a nucleotide oligomerization domain 1(NOD1) polymorphim and NOD2 mutant alleles on crohn´s disease phenotype. World J Gastroenterol 2007;13:5446-53.

48. Chamaillard M, Philpott D, Girardin SE, et al. Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci U S A. 2003;100:3455-60.

49. Strober W, Asano N, Fuss I, Kitani A, Watanabe T. Cellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms in crohn’s disease. Immunol Rev. 2014;260: 249-60.

50. Inohara N, Nuñez G. NODs: Intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol. 2003;3:371-82.

51. Sales-Marques C, Salomão H, Fava VM, et al. NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians. Hum Genet. 2014;133:1525-32.

52. Grube M, Brenmoehl J, Rogler G, Hahn J, Herr W, Holler E. Donor Nucleotide-Binding oligomerization-containing protein 2 (NOD2) single nucleotide polymorphism 13 is associated with septic shock after allogenic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1399-404.

53. Zhang Q, Pan Y, Yan R, et al. Commensal bacteria direct selective cargo sorting to promote symbiosis. Nat Immunol. 2015;16: 918-26.

54. Salem M, Seidelin JB, Eickhardt S, et al. Species-specific engagement of human nucleotide oligomerization domain 2 (NOD)2 and toll-like receptor (TLR) signalling upon intracellular bacterial infection: Role of crohn’s associated NOD2 gene variants. Clin Exp Immunol. 2015;179:426-34.

55. Franchi L, Núñez G. The nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol. 2008;38:2085-9.

56. Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA. Crucial role for the nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453:1122-6.

57. Geddes K, Magalhães JG, Girardin SE. Unleashing the therapeutic potential of NOD-like receptors. Nat Rev Drug Discov. 2009;8:465-79.

58. Kool M, Soullié T, van Nimwegen M, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008;205:869-82.

59. Canning P, Ruan Q, Schwerd T, et al. Inflammatory signaling by NOD-RIPK2 is inhibited by clinically relevant type II kinase inhibitors. Chem Biol. 2015;22:1174-84.