Implication of Toll/IL-1 Receptor Domain Containing Adapters in -induced Inflammation

Overview

Journal Innate Immun

Publisher Sage Publications

Specialties Allergy & Immunology
Microbiology

Date 2021 May 21

PMID 34018827

Citations 1

Authors

Isaac M Bugueno

Nadia Benkirane-Jessel

Olivier Huck

Affiliations

Soon will be listed here.

Abstract

Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a involvement, such as atherothrombosis.

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References

Kassebaum N, Bernabe E, Dahiya M, Bhandari B, Murray C, Marcenes W . Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014; 93(11):1045-53. PMC: 4293771. DOI: 10.1177/0022034514552491. View

Qiu J, Nie Y, Zhao Y, Zhang Y, Li L, Wang R . Safeguarding intestine cells against enteropathogenic by intracellular protein reaction, a preventive antibacterial mechanism. Proc Natl Acad Sci U S A. 2020; 117(10):5260-5268. PMC: 7071885. DOI: 10.1073/pnas.1914567117. View

Elkaim R, Werner S, Kocgozlu L, Tenenbaum H . P. gingivalis regulates the expression of Cathepsin B and Cystatin C. J Dent Res. 2008; 87(10):932-6. DOI: 10.1177/154405910808701010. View

ONeill L, Bowie A . The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007; 7(5):353-64. DOI: 10.1038/nri2079. View

Abusleme L, Dupuy A, Dutzan N, Silva N, Burleson J, Strausbaugh L . The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J. 2013; 7(5):1016-25. PMC: 3635234. DOI: 10.1038/ismej.2012.174. View

Mai J, Virtue A, Shen J, Wang H, Yang X . An evolving new paradigm: endothelial cells--conditional innate immune cells. J Hematol Oncol. 2013; 6:61. PMC: 3765446. DOI: 10.1186/1756-8722-6-61. View

Elkaim R, Dahan M, Kocgozlu L, Werner S, Kanter D, Kretz J . Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic plaques and healthy blood vessels: a preliminary study. J Periodontal Res. 2008; 43(2):224-31. DOI: 10.1111/j.1600-0765.2007.01018.x. View

Mysak J, Podzimek S, Sommerova P, Lyuya-Mi Y, Bartova J, Janatova T . Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. 2014; 2014:476068. PMC: 3984870. DOI: 10.1155/2014/476068. View

Diaz L, Hoare A, Soto C, Bugueno I, Silva N, Dutzan N . Changes in lipopolysaccharide profile of Porphyromonas gingivalis clinical isolates correlate with changes in colony morphology and polymyxin B resistance. Anaerobe. 2015; 33:25-32. DOI: 10.1016/j.anaerobe.2015.01.009. View

10.

Shang L, Deng D, Buskermolen J, Roffel S, Janus M, Krom B . Commensal and Pathogenic Biofilms Alter Toll-Like Receptor Signaling in Reconstructed Human Gingiva. Front Cell Infect Microbiol. 2019; 9:282. PMC: 6692492. DOI: 10.3389/fcimb.2019.00282. View

11.

Hirsch J, Eslamizar L, Filanoski B, Malekzadeh N, Haugland R, Beechem J . Easily reversible desthiobiotin binding to streptavidin, avidin, and other biotin-binding proteins: uses for protein labeling, detection, and isolation. Anal Biochem. 2002; 308(2):343-57. DOI: 10.1016/s0003-2697(02)00201-4. View

12.

Spahr A, Klein E, Khuseyinova N, Boeckh C, Muche R, Kunze M . Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study. Arch Intern Med. 2006; 166(5):554-9. DOI: 10.1001/archinte.166.5.554. View

13.

Huck O, Elkaim R, Davideau J, Tenenbaum H . Porphyromonas gingivalis-impaired innate immune response via NLRP3 proteolysis in endothelial cells. Innate Immun. 2014; 21(1):65-72. DOI: 10.1177/1753425914523459. View

14.

Verstak B, Nagpal K, Bottomley S, Golenbock D, Hertzog P, Mansell A . MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses. J Biol Chem. 2009; 284(36):24192-203. PMC: 2782013. DOI: 10.1074/jbc.M109.023044. View

15.

Gabarrini G, Grasso S, van Winkelhoff A, van Dijl J . Gingimaps: Protein Localization in the Oral Pathogen . Microbiol Mol Biol Rev. 2020; 84(1). PMC: 6941882. DOI: 10.1128/MMBR.00032-19. View

16.

Pan C, Xu X, Tan L, Lin L, Pan Y . The effects of Porphyromonas gingivalis on the cell cycle progression of human gingival epithelial cells. Oral Dis. 2013; 20(1):100-8. DOI: 10.1111/odi.12081. View

17.

Mulhall H, Huck O, Amar S . , a Long-Range Pathogen: Systemic Impact and Therapeutic Implications. Microorganisms. 2020; 8(6). PMC: 7357039. DOI: 10.3390/microorganisms8060869. View

18.

Socransky S, Haffajee A, Cugini M, Smith C, Kent Jr R . Microbial complexes in subgingival plaque. J Clin Periodontol. 1998; 25(2):134-44. DOI: 10.1111/j.1600-051x.1998.tb02419.x. View

19.

Rosenfeld M, Campbell L . Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost. 2011; 106(5):858-67. DOI: 10.1160/TH11-06-0392. View

20.

Panneerselvam P, Singh L, Ho B, Chen J, Ding J . Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence. Biochem J. 2011; 442(2):263-71. DOI: 10.1042/BJ20111653. View