Immunological Roles of NLR in Allergic Diseases and Its Underlying Mechanisms

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Feb 6

PMID 33546184

Citations 7

Authors

Miranda Sin-Man Tsang

Tianheng Hou

Ben Chung-Lap Chan

Chun Kwok Wong

Affiliations

Soon will be listed here.

Abstract

Our understanding on the immunological roles of pathogen recognition in innate immunity has vastly increased over the past 20 years. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLR) are cytosolic pattern recognition receptors (PRR) that are responsible for sensing microbial motifs and endogenous damage signals in mammalian cytosol for immune surveillance and host defense. The accumulating discoveries on these NLR sensors in allergic diseases suggest that the pathogenesis of allergic diseases may not be confined to the adaptive immune response. Therapy targeting NLR in murine models also shields light on its potential in the treatment of allergies in man. In this review, we herein summarize the recent understanding of the role of NLR sensors and their molecular mechanisms involved in allergic inflammation, including atopic dermatitis and allergic asthma.

Citing Articles

Neutrophil-to-lymphocyte ratio, platelets-to-lymphocyte ratio, and red cell distribution width as prognostic indicators for length of hospital stay in pediatric asthma.

Eltyeb E, Gohal G, Alhazmi S, Alqassim M, Hakami E, Moafa M Saudi Med J. 2025; 46(2):143-149.

PMID: 39933761 PMC: 11822938. DOI: 10.15537/smj.2025.46.2.20240934.

Regulating Immune Responses Induced by PEGylated Messenger RNA-Lipid Nanoparticle Vaccine.

Jo H, Jeoung J, Kim W, Jeoung D Vaccines (Basel). 2025; 13(1).

PMID: 39852793 PMC: 11768904. DOI: 10.3390/vaccines13010014.

A Review on Asthma and Allergy: Current Understanding on Molecular Perspectives.

Gohal G, Moni S, Bakkari M, Elmobark M J Clin Med. 2024; 13(19).

PMID: 39407835 PMC: 11476424. DOI: 10.3390/jcm13195775.

Gu-Ben-Hua-Shi (AESS) formula ameliorates atopic dermatitis via regulating NLRP3 signaling pathways.

Li X, Feng L, Zhong T, Mo X, Wang D, Gu J Saudi Pharm J. 2023; 31(11):101792.

PMID: 37841059 PMC: 10571024. DOI: 10.1016/j.jsps.2023.101792.

Severe Acute Bronchial Asthma with Sepsis: Determining the Status of Biomarkers in the Diagnosis of the Disease.

Sinha S, Kumar S, Narwaria M, Singh A, Haque M Diagnostics (Basel). 2023; 13(16).

PMID: 37627950 PMC: 10453001. DOI: 10.3390/diagnostics13162691.

References

Ogura Y, Bonen D, Inohara N, Nicolae D, Chen F, Ramos R . A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001; 411(6837):603-6. DOI: 10.1038/35079114. View

Rosenstiel P, Huse K, Till A, Hampe J, Hellmig S, Sina C . A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor of NOD2/receptor-interacting protein kinase 2-induced signaling pathways. Proc Natl Acad Sci U S A. 2006; 103(9):3280-5. PMC: 1413865. DOI: 10.1073/pnas.0505423103. View

Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L . An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol. 2003; 4(7):702-7. DOI: 10.1038/ni945. View

Liu X, Shen J, Fan D, Qiu X, Guo Q, Zheng K . Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice. Front Pharmacol. 2018; 8:944. PMC: 5743824. DOI: 10.3389/fphar.2017.00944. View

Xu M, Wang L, Wang M, Wang H, Zhang H, Chen Y . Mitochondrial ROS and NLRP3 inflammasome in acute ozone-induced murine model of airway inflammation and bronchial hyperresponsiveness. Free Radic Res. 2019; 53(7):780-790. DOI: 10.1080/10715762.2019.1630735. View

Douglas T, Champagne C, Morizot A, Lapointe J, Saleh M . The Inflammatory Caspases-1 and -11 Mediate the Pathogenesis of Dermatitis in Sharpin-Deficient Mice. J Immunol. 2015; 195(5):2365-73. DOI: 10.4049/jimmunol.1500542. View

Gross O, Poeck H, Bscheider M, Dostert C, Hannesschlager N, Endres S . Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature. 2009; 459(7245):433-6. DOI: 10.1038/nature07965. View

Tada H, Aiba S, Shibata K, Ohteki T, Takada H . Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper type 1 cells. Infect Immun. 2005; 73(12):7967-76. PMC: 1307098. DOI: 10.1128/IAI.73.12.7967-7976.2005. View

Herberth G, Offenberg K, Rolle-Kampczyk U, Bauer M, Otto W, Roder S . Endogenous metabolites and inflammasome activity in early childhood and links to respiratory diseases. J Allergy Clin Immunol. 2015; 136(2):495-7. DOI: 10.1016/j.jaci.2015.01.022. View

10.

Kvarnhammar A, Petterson T, Cardell L . NOD-like receptors and RIG-I-like receptors in human eosinophils: activation by NOD1 and NOD2 agonists. Immunology. 2011; 134(3):314-25. PMC: 3209571. DOI: 10.1111/j.1365-2567.2011.03492.x. View

11.

Allen I, Lich J, Arthur J, Jania C, Roberts R, Callaway J . Characterization of NLRP12 during the development of allergic airway disease in mice. PLoS One. 2012; 7(1):e30612. PMC: 3264608. DOI: 10.1371/journal.pone.0030612. View

12.

Gamelas Magalhaes J, Fritz J, Le Bourhis L, Sellge G, Travassos L, Selvanantham T . Nod2-dependent Th2 polarization of antigen-specific immunity. J Immunol. 2008; 181(11):7925-35. DOI: 10.4049/jimmunol.181.11.7925. View

13.

Caruso R, Warner N, Inohara N, Nunez G . NOD1 and NOD2: signaling, host defense, and inflammatory disease. Immunity. 2014; 41(6):898-908. PMC: 4272446. DOI: 10.1016/j.immuni.2014.12.010. View

14.

Kankkunen P, Teirila L, Rintahaka J, Alenius H, Wolff H, Matikainen S . (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J Immunol. 2010; 184(11):6335-42. DOI: 10.4049/jimmunol.0903019. View

15.

Borghini S, Tassi S, Chiesa S, Caroli F, Carta S, Caorsi R . Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum. 2011; 63(3):830-9. PMC: 3112487. DOI: 10.1002/art.30170. View

16.

Netea M, Schlitzer A, Placek K, Joosten L, Schultze J . Innate and Adaptive Immune Memory: an Evolutionary Continuum in the Host's Response to Pathogens. Cell Host Microbe. 2019; 25(1):13-26. DOI: 10.1016/j.chom.2018.12.006. View

17.

Duan W, Mehta A, Magalhaes J, Ziegler S, Dong C, Philpott D . Innate signals from Nod2 block respiratory tolerance and program T(H)2-driven allergic inflammation. J Allergy Clin Immunol. 2010; 126(6):1284-93.e10. PMC: 3058679. DOI: 10.1016/j.jaci.2010.09.021. View

18.

Tomani J, Gainkam L, Nshutiyayesu S, Mukazayire M, Oliveira Ribeiro S, Stevigny C . An ethnobotanical survey and inhibitory effects on NLRP3 inflammasomes/Caspase-1 of herbal recipes' extracts traditionally used in Rwanda for asthma treatment. J Ethnopharmacol. 2018; 227:29-40. DOI: 10.1016/j.jep.2018.08.016. View

19.

Heymann P, Carper H, Murphy D, Platts-Mills T, Patrie J, McLaughlin A . Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol. 2004; 114(2):239-47. PMC: 7185400. DOI: 10.1016/j.jaci.2004.04.006. View

20.

Kapoor S, Patel S, Kartan S, Axelrod D, Capitle E, Rameshwar P . Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy-induced asthma. J Allergy Clin Immunol. 2011; 129(4):1094-101. DOI: 10.1016/j.jaci.2011.10.048. View