The Expression and Function of Nod-like Receptors in Neutrophils

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2009 Dec 17

PMID 20002790

Citations 41

Authors

Anna-Karin Ekman

Lars Olaf Cardell

Affiliations

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Abstract

Neutrophils make up an essential part of the innate immune system, and are involved both in the initial responses to pathogens, and in orchestrating later immune responses. Neutrophils recognize pathogens through pattern-recognition receptors (PRRs), which are activated by microbial motifs. The Nod-like receptors (nucleotide-binding domain leucine-rich repeat containing family; NLRs) constitute a recently discovered group of PRRs whose role in the neutrophil immune responses is not yet characterized. The present study aimed to investigate the expression and function of NLRs in neutrophils. Neutrophils were isolated from human peripheral blood, and the presence of nucleotide-binding oligomerization domain 1 (NOD1), NOD2 and NACHT-LRR-PYD-containing protein 3 (NLRP3) was evaluated with flow cytometry and immunohistochemistry. The expression of NOD1, NOD2 and NLRP3 messenger RNA was determined using real-time reverse transcription-polymerase chain reaction. Changes in neutrophil cytokine secretion, phenotype and migration following agonist-induced activation were studied using enzyme-linked immunosorbent assay, flow cytometry and a chemotaxis assay, respectively. No expression of NOD1 was found in isolated neutrophils and stimulation with the NOD1 ligand gamma-d-glutamyl-meso-diaminopimelic acid induced no signs of activity. In contrast, a marked expression of NOD2 and NLRP3 was found. NOD2 activation with MurNAc-l-Ala-d-isoGln (MDP) resulted in interleukin-8 secretion, CD62 ligand down-regulation, CD11b up-regulation and increased migration towards an inflammatory stimulus. NLRP3 activation with alum caused interleukin-1beta secretion and facilitated migration. Altogether, this suggests that NLRs may be a previously unknown pathway for neutrophil activation.

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References

Sabroe I, Prince L, Jones E, Horsburgh M, Foster S, Vogel S . Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span. J Immunol. 2003; 170(10):5268-75. DOI: 10.4049/jimmunol.170.10.5268. View

Hysi P, Kabesch M, Moffatt M, Schedel M, Carr D, Zhang Y . NOD1 variation, immunoglobulin E and asthma. Hum Mol Genet. 2005; 14(7):935-41. DOI: 10.1093/hmg/ddi087. View

Tattoli I, Travassos L, Carneiro L, Magalhaes J, Girardin S . The Nodosome: Nod1 and Nod2 control bacterial infections and inflammation. Semin Immunopathol. 2007; 29(3):289-301. DOI: 10.1007/s00281-007-0083-2. View

Rietdijk S, Burwell T, Bertin J, Coyle A . Sensing intracellular pathogens-NOD-like receptors. Curr Opin Pharmacol. 2008; 8(3):261-6. DOI: 10.1016/j.coph.2008.04.003. View

Franchi L, Park J, Shaw M, Marina-Garcia N, Chen G, Kim Y . Intracellular NOD-like receptors in innate immunity, infection and disease. Cell Microbiol. 2007; 10(1):1-8. DOI: 10.1111/j.1462-5822.2007.01059.x. View

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

Schumann R, Tapping R . Genomic variants of TLR1--it takes (TLR-)two to tango. Eur J Immunol. 2007; 37(8):2059-62. DOI: 10.1002/eji.200737604. View

Mansson A, Cardell L . Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils. J Leukoc Biol. 2009; 85(4):719-27. DOI: 10.1189/jlb.0808494. 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

10.

Lee M, Kim Y . Pattern-recognition receptor signaling initiated from extracellular, membrane, and cytoplasmic space. Mol Cells. 2007; 23(1):1-10. View

11.

Mann B, Chung K . Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy. Respir Res. 2006; 7:59. PMC: 1458332. DOI: 10.1186/1465-9921-7-59. View

12.

Fransson M, Benson M, Erjefalt J, Jansson L, Uddman R, Bjornsson S . Expression of Toll-like receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis. Respir Res. 2007; 8:17. PMC: 1810251. DOI: 10.1186/1465-9921-8-17. View

13.

Wiken M, Grunewald J, Eklund A, Wahlstrom J . Higher monocyte expression of TLR2 and TLR4, and enhanced pro-inflammatory synergy of TLR2 with NOD2 stimulation in sarcoidosis. J Clin Immunol. 2008; 29(1):78-89. DOI: 10.1007/s10875-008-9225-0. View

14.

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

15.

Kim Y, Park J, Shaw M, Franchi L, Inohara N, Nunez G . The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity. 2008; 28(2):246-57. DOI: 10.1016/j.immuni.2007.12.012. View

16.

Kufer T . Signal transduction pathways used by NLR-type innate immune receptors. Mol Biosyst. 2008; 4(5):380-6. DOI: 10.1039/b718948f. View

17.

Palsson-McDermott E, ONeill L . Building an immune system from nine domains. Biochem Soc Trans. 2007; 35(Pt 6):1437-44. DOI: 10.1042/BST0351437. View

18.

Hayashi F, Means T, Luster A . Toll-like receptors stimulate human neutrophil function. Blood. 2003; 102(7):2660-9. DOI: 10.1182/blood-2003-04-1078. View

19.

Fritz J, Girardin S, Fitting C, Werts C, Mengin-Lecreulx D, Caroff M . Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur J Immunol. 2005; 35(8):2459-70. DOI: 10.1002/eji.200526286. View

20.

Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M . Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol. 2008; 181(6):3755-9. DOI: 10.4049/jimmunol.181.6.3755. View