Secrets and Lies of Host-microbial Interactions: MHC Restriction and Trans-regulation of T Cell Trafficking Conceal the Role of Microbial Agents on the Edge Between Health and Multifactorial/complex Diseases

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2024 Jan 12

PMID 38216734

Authors

F Ria

G Delogu

L Ingrosso

M Sali

G Di Sante

Affiliations

Soon will be listed here.

Abstract

Here we critically discuss data supporting the view that microbial agents (pathogens, pathobionts or commensals alike) play a relevant role in the pathogenesis of multifactorial diseases, but their role is concealed by the rules presiding over T cell antigen recognition and trafficking. These rules make it difficult to associate univocally infectious agents to diseases' pathogenesis using the paradigm developed for canonical infectious diseases. (Cross-)recognition of a variable repertoire of epitopes leads to the possibility that distinct infectious agents can determine the same disease(s). There can be the need for sequential infection/colonization by two or more microorganisms to develop a given disease. Altered spreading of infectious agents can determine an unwanted activation of T cells towards a pro-inflammatory and trafficking phenotype, due to differences in the local microenvironment. Finally, trans-regulation of T cell trafficking allows infectious agents unrelated to the specificity of T cell to modify their homing to target organs, thereby driving flares of disease. The relevant role of microbial agents in largely prevalent diseases provides a conceptual basis for the evaluation of more specific therapeutic approaches, targeted to prevent (vaccine) or cure (antibiotics and/or Biologic Response Modifiers) multifactorial diseases.

References

Furusawa Y, Obata Y, Fukuda S, Endo T, Nakato G, Takahashi D . Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013; 504(7480):446-50. DOI: 10.1038/nature12721. View

Zegarra-Ruiz D, Kim D, Norwood K, Kim M, Wu W, Saldana-Morales F . Thymic development of gut-microbiota-specific T cells. Nature. 2021; 594(7863):413-417. PMC: 8323488. DOI: 10.1038/s41586-021-03531-1. View

Wells P, Williams F, Matey-Hernandez M, Menni C, Steves C . 'RA and the microbiome: do host genetic factors provide the link?. J Autoimmun. 2019; 99:104-115. PMC: 6470121. DOI: 10.1016/j.jaut.2019.02.004. View

Cencioni M, Mattoscio M, Magliozzi R, Bar-Or A, Muraro P . B cells in multiple sclerosis - from targeted depletion to immune reconstitution therapies. Nat Rev Neurol. 2021; 17(7):399-414. DOI: 10.1038/s41582-021-00498-5. View

Hirako I, Ataide M, Faustino L, Assis P, Sorensen E, Ueta H . Splenic differentiation and emergence of CCR5CXCL9CXCL10 monocyte-derived dendritic cells in the brain during cerebral malaria. Nat Commun. 2016; 7:13277. PMC: 5097164. DOI: 10.1038/ncomms13277. View

Salaman M, Gould K . Breakdown of T-cell ignorance: The tolerance failure responsible for mainstream autoimmune diseases?. J Transl Autoimmun. 2020; 3:100070. PMC: 7695872. DOI: 10.1016/j.jtauto.2020.100070. View

Scher J, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A . Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012; 64(10):3083-94. PMC: 3428472. DOI: 10.1002/art.34539. View

Zhang Q, Guo Y, Zhang B, Liu H, Peng Y, Wang D . Identification of hub biomarkers of myocardial infarction by single-cell sequencing, bioinformatics, and machine learning. Front Cardiovasc Med. 2022; 9:939972. PMC: 9357907. DOI: 10.3389/fcvm.2022.939972. View

Totaro M, Cattani P, Ria F, Tolusso B, Gremese E, Fedele A . Porphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue. Arthritis Res Ther. 2013; 15(3):R66. PMC: 4060366. DOI: 10.1186/ar4243. View

10.

Chen B, Zhao Y, Li S, Yang L, Wang H, Wang T . Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening. Sci Rep. 2018; 8(1):17126. PMC: 6244360. DOI: 10.1038/s41598-018-35473-6. View

11.

Penitente R, Nicolo C, van den Elzen P, Di Sante G, Agrati C, Aloisi F . Administration of PLP139-151 primes T cells distinct from those spontaneously responsive in vitro to this antigen. J Immunol. 2008; 180(10):6611-22. DOI: 10.4049/jimmunol.180.10.6611. View

12.

Malferrari G, Stella A, MONFERINI E, Saltini G, Proverbio M, Grimaldi L . Ctla4 and multiple sclerosis in the Italian population. Exp Mol Pathol. 2004; 78(1):55-7. DOI: 10.1016/j.yexmp.2004.10.001. View

13.

Garin T, Rubinstein A, Grigoriadis N, Nedvetzki S, Abramsky O, Mizrachi-Koll R . CD44 variant DNA vaccination with virtual lymph node ameliorates experimental autoimmune encephalomyelitis through the induction of apoptosis. J Neurol Sci. 2007; 258(1-2):17-26. DOI: 10.1016/j.jns.2007.01.079. View

14.

Wilson C, Tiwana H, Ebringer A . Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity. Microbes Infect. 2000; 2(12):1489-96. DOI: 10.1016/s1286-4579(00)01303-4. View

15.

Asgharzadeh M, Jigheh Z, Kafil H, Farhoudi M, Oskouei D, Khaki-Khatibi F . Association of Interleukin-1 and Inteleukin-1 Receptor Antagonist Gene Polymorphisms with Multiple Sclerosis in Azeri Population of Iran. Endocr Metab Immune Disord Drug Targets. 2020; 20(7):1110-1116. DOI: 10.2174/1871530320666200309142541. View

16.

Quirke A, Lugli E, Wegner N, Hamilton B, Charles P, Chowdhury M . Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis. Ann Rheum Dis. 2013; 73(1):263-9. PMC: 3888615. DOI: 10.1136/annrheumdis-2012-202726. View

17.

Sospedra M, Martin R . Molecular mimicry in multiple sclerosis. Autoimmunity. 2006; 39(1):3-8. DOI: 10.1080/08916930500484922. View

18.

Kontou P, Pavlopoulou A, Braliou G, Bogiatzi S, Dimou N, Bangalore S . Identification of gene expression profiles in myocardial infarction: a systematic review and meta-analysis. BMC Med Genomics. 2018; 11(1):109. PMC: 6260684. DOI: 10.1186/s12920-018-0427-x. View

19.

Mawanda F, Wallace R . Can infections cause Alzheimer's disease?. Epidemiol Rev. 2013; 35:161-80. PMC: 4707877. DOI: 10.1093/epirev/mxs007. View

20.

Arribas-Layton D, Guyer P, Delong T, Dang M, Chow I, Speake C . Hybrid Insulin Peptides Are Recognized by Human T Cells in the Context of DRB1*04:01. Diabetes. 2020; 69(7):1492-1502. PMC: 7306133. DOI: 10.2337/db19-0620. View