Intestinal microbiota composition and peripheral blood Th cell subsets in patients with multiple sclerosis

Cover Page

Cite item

Abstract

At present, the role of intestinal microbiota in diverse diseases of the central nervous system, including of multiple sclerosis (MS) has been extensively investigated. Self-reactive CD4+ Th1 and Th17 cells specific to myelin-derived antigens play a key role in the MS pathogenesis. Taking into consideration pathogenetic features related to MS development, we examined a relation between intestinal microbiocenosis and abundance of various peripheral blood helper T (Th) cell subsets in MS patients. Objective of the study: to assess prevalence of individual members of the intestinal microbiota in MS patients and analyze a relation with peripheral blood Th cell subsets. Prevalence of symbiotic and opportunistic microbial species was estimated by bacteriological method and real time PCR in 112 MS patients (72 females, 40 males) of varying severity and duration. Th cell subsets (Th1, Th2, Th17, Th1/Th17, Th17/Th22, DP Th17) were analyzed by using multi-color flow cytometry based on Th cell subset-specific surface expression of chemokine receptors. A relationship between individual intestinal microbiota species and severity, duration and rate of MS progression, as well as with the phenotype of immune cells was assessed. It was found that the most significant correlation between percentage of peripheral blood Th cell subsets was observed with prevalence of Lactobacillus spp., Enterococcus spp. and Enterobacter spp. Moreover, prevalence of Enterococcus spp. Th cell composition influenced synergistically or antagonistically together with Enterobacter spp. or Lactobacillus spp., respectively. It is suggested that direct and indirect impact of intestinal microbiota composition on human immune system might contribute to developing novel strategies for treating MS.

About the authors

I. N. Abdurasulova

Institute of Experimental Medicine;
St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: i_abdurasulova@mail.ru

PhD (Biology), Leading Researcher, Pavlov Department of Physiology;

Associate Professor, Department of Medical Biophysics, 

197376, St. Petersburg, Akademika Pavlova str., 12

Russian Federation

E. A. Tarasova

Institute of Experimental Medicine

Email: tarasovahellen@mail.ru

Researcher, Pavlov Department of Physiology,

St. Petersburg

Russian Federation

I. V. Kudryavtsev

Institute of Experimental Medicine;
Pavlov First St. Petersburg State Medical University

Email: igorek1981@yandex.ru

PhD (Biology), Senior Researcher, Laboratory of Immunology;

Associate Professor, Department of Immunology,

St. Petersburg

Russian Federation

I. G. Negoreeva

Institute of the Human Brain RAS

Email: nip@ihb.spb.ru

PhD (Medicine), Researcher, Laboratory of Neuroimmunology,

St. Petersburg

Russian Federation

A. G. Ilves

Institute of the Human Brain RAS

Email: ailves@hotmail.com

PhD (Medicine), Senior Researcher, Laboratory of Neuroimmunology,

St. Petersburg

Russian Federation

M. K. Serebriakova

Institute of Experimental Medicine

Email: m-serebryakova@yandex.ru

Researcher, Department of Immunology,

St. Petersburg

Russian Federation

E. I. Ermolenko

Institute of Experimental Medicine
St. Petersburg State University

Email: lermolenko1@yandex.ru

PhD, MD (Medicine), Head of the Laboratory of Biomedical Microecology,

St. Petersburg

Russian Federation

E. V. Ivashkova

Institute of the Human Brain RAS

Email: ivashkova@ihb.spb.ru

PhD (Medicine), Researcher, Laboratory of Neuroimmunology,

St. Petersburg

Russian Federation

A. V. Matsulevich

Institute of Experimental Medicine

Email: cat_fly@bk.ru

Researcher, Pavlov Department of Physiology,

St. Petersburg

Russian Federation

A. E. Tatarinov

Institute of Experimental Medicine

Email: alex2ta@mail.ru

Head of the Neurological Department, Institute of Experimental Medicine,

St. Petersburg

Russian Federation

I. D. Stoliarov

Institute of the Human Brain RAS

Email: sid@ihb.spb.ru

PhD, MD (Medicine), Professor, Head of Laboratory of Neuroimmunology,

St. Petersburg

Russian Federation

V. M. Klimenko

Institute of Experimental Medicine

Email: klimenko_victor@mail.ru

PhD, MD (Medicine), Professor, Head of Pavlov Department of Physiology, 

St. Petersburg

Russian Federation

A. N. Suvorov

Institute of Experimental Medicine;
St. Petersburg State University

Email: alexaner_suvorov1@hotmail.com

Head of the Department of Molecular Microbiology;

RAS Corresponding Member, PhD, MD (Medicine), Professor, Head of the Department of Fundamental Problems of Medicine and Medical Technologies, Faculty of Dentistry and Medical Technologies,

St. Petersburg

Russian Federation

References

  1. Абдурасулова И.Н., Тарасова Е.А., Ермоленко Е.И., Елисеев А.В., Мацулевич А.В., Бисага Г.Н., Скулябин Д.И., Суворов А.Н., Клименко В.М. При рассеянном склерозе изменяется качественный и количественный состав микробиоты кишечника // Медицинский академический журнал. 2015. Т. 15, № 3. С. 55–67.
  2. Абдурасулова И.Н., Тарасова Е.А., Мацулевич А.В., Елисеев А.В., Ермоленко Е.И., Суворов А.Н., Клименко В.М. Изменение качественного и количественного состава кишечной микробиоты у крыс при экспериментальном аллергическом энцефаломиелите // Российский физиологический журнал им. И.М. Сеченова. 2015. Т. 101, № 11. С. 1235–1249.
  3. Абдурасулова И.Н., Ермоленко Е.И., Мацулевич А.В., Абдурасулова К.О., Тарасова Е.А., Кудрявцев И.В., Бисага Г.Н., Суворов А.Н., Клименко В.М. Влияние пробиотических энтерококков и глатирамера ацетат на тяжесть экспериментального аллергического энцефаломиелита у крыс // Российский физиологический журнал им. И.М. Сеченова. 2016. Т. 102, № 4. С. 463–479. doi: 10.1007/s11055-017-0484-1 (In Russ.)
  4. Абдурасулова И.Н., Тарасова Е.А., Никифорова И.Г., Ильвес А.Г., Ивашкова Е.В., Мацулевич А.В., Татаринов А.Е., Шангина Л.В., Ермоленко Е.И., Клименко В.М., Столяров И.Д., Суворов А.Н. Особенности состава микробиоты кишечника у пациентов с рассеянным склерозом, получающих разные ПИТРС // Журнал неврологии и психиатрии им. С.С. Корсакова. 2018. Т. 118, № 8, вып. 2. С. 62–69. doi: 10.17116/jnevro201811808262 (In Russ.)
  5. Кудрявцев И.В., Борисов А.Г., Кробинец И.И., Савченко А.А., Серебрякова М.К., Тотолян А.А. Хемокиновые рецепторы на Т-хелперах различного уровня дифференцировки: основные субпопуляции // Медицинская иммунология. 2016. Т. 18, № 3. С. 239–250. doi: 10.15789/1563-0625-2016-3-239-250 (In Russ.)
  6. Кудрявцев И.В., Ильвес А.Г., Борисов А.Г., Минеев К.К., Петров А.М., Савченко А.А., Серебрякова М.К., Столяров И.Д. CCR6-позитивные Т-хелперы периферической крови при рассеянном склерозе // Цитокины и воспаление. 2016. Т. 15, № 2. С. 166–172.
  7. Кудрявцев И.В., Савицкий В.П. Многоцветный анализ основных субпопуляций Т-хелперов и цитотоксических Т-клеток методом проточной цитофлуориметрии // Российский иммунологический журнал. 2012. Т. 6 (14), № 3 (1). С. 94–97.
  8. Хайдуков С.В., Байдун Л.А., Зурочка А.В., Тотолян А.А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» (проект) // Медицинская иммунология. 2012. Т. 14, № 3. С. 255–268. doi: 10.15789/1563-0625-2012-3-255-268 (In Russ.)
  9. Шендеров Б.А., Голубев В.Л., Данилов А.Б., Прищепа А.В. Кишечная микробиота человека и нейродегенеративные заболевания // Поликлиника. 2016. № 1 (cпецвыпуск). С. 7–13.
  10. Abdurasulova I.N., Matsulevich A.V., Tarasova E.A., Kudrjavtsev I.V., Serebrjakova M.K., Ermolenko E.I., Bisaga G.N., Klimenko V.M., Suvorov A.N. Enterococcus faecium L3 and glatiramer acetate ameliorate of experimental allergic encephalomyelitis (EAE) in rats by affecting different populations of immune cells. Beneficial Microbes, 2016, vol. 7, no. 5, pp. 719–729. doi: 10.3920/BM2016.0018
  11. Annunziato F., Cosmi L., Liotta F., Maggi E., Romagnani S. Main features of human T helper 17 cells. Ann. NY Acad. Sci., 2013, vol. 1284, pp. 66–70. doi: 10.1111/nyas.12075
  12. Aranami T., Yamamura T. Th17 Cells and autoimmune encephalomyelitis (EAE/MS). Allergol. Int., 2008, vol. 57, no. 2, pp. 115–120. doi: 10.2332/allergolint.R-07-159
  13. Askarian F., Wagner T., Johannessen M., Nizet V. Staphylococcus aureus modulation of innate immune responses through Tolllike (TLRs), (NOD)-like (NLRs) and C-type lectin (CLRs) receptors. FEMS Microbiol. Rev., 2018. doi: 10.1093/femsre/fuy025
  14. Atarashi K., Nishimura J., Shima T., Umesaki Y., Yamamoto M., Onoue M., Yagita H., Ishii N., Evans R., Honda K., Takeda K. ATP drives lamina propria T(H)17 cell differentiation. Nature, 2008, vol. 455, no. 7214, pp. 808–812. doi: 10.1038/nature07240
  15. Atarashi K., Tanoue T., Shima T., Imaoka A., Kuwahara T., Momose Y., Cheng G., Yamasaki S., Saito T., Ohba Y., Taniguchi T., Takeda K., Hori S., Ivanov I.I., Umesaki Y., Itoh K., Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science, 2011, vol. 331, no. 6015, pp. 337–341. doi: 10.1126/science.1198469
  16. Aujla S.J., Chan Y.R., Zheng M., Fei M., Askew D.J., Pociask D.A., Reinhart T.A., McAllister F., Edeal J., Gaus K., Husain S., Kreindler J.L., Dubin P.J., Pilewski J.M., Myerburg M.M., Mason C.A., Iwakura Y., Kolls J.K. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med., 2008, vol. 14, no. 3, pp. 275–281. doi: 10.1038/nm1710
  17. Basu R., O’Quinn D.B., Silberger D.J., Schoeb T.R., Fouser L., Ouyang W., Hatton R.D., Weaver C.T. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity, 2012, vol. 37, no. 6, pp. 1061–1075. doi: 10.1016/j.immuni.2012.08.024
  18. Benito-Leon J., Pisa D., Alonso R., Calleja P., Diaz-Sanchez M., Carrasco L. Association between multiple sclerosis and Candida species: evidence from a case-control study. Eur. J. Clin. Microbiol. Infect. Dis., 2010, vol. 29, no. 9, pp. 1139–1145. doi: 10.1007/s10096-010-0979-y
  19. Berer K., Mues M., Koutrolos M., Al Rasbi Z., Boziki M., Johner C., Wekerle H., Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature, 2011, vol. 479, pp. 538–541. doi: 10.1038/nature10554
  20. Berer K., Gerdes L.A., Cekanaviciute E., Jia X., Xiao L., Xia Z., Liu C., Klotz L., Stauffer U., Baranzini S.E., Kümpfel T., Hohlfeld R., Krishnamoorthy G., Wekerle H. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc. Natl. Acad. Sci. USA, 2017, vol. 114, no. 40, pp. 10719–10724. doi: 10.1073/pnas.1711233114
  21. Brucklacher-Waldert V., Stuerner K., Kolster M., Wolthausen J., Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain J. Neurol., 2009, vol. 132, iss. 12, pp. 3329–3341. doi: 10.1093/brain/awp289
  22. Buscarinu M.C., Cerasoli B., Annibali V., Policano C., Lionetto L., Capi M., Mechelli R., Romano S., Fornasiero A., Mattei G., Piras E., Angelini D.F., Battistini L., Simmaco M., Umeton R., Salvetti M., Ristori G. Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: a pilot study. Multiple Sclerosis, 2017, vol. 23, no. 3, pp. 442–446. doi: 10.1177/1352458516652498
  23. Cekanaviciute E., Yoo B.B., Runia T.F., Debelius J.W., Singh S., Nelson C.A., Kanner R., Bencosme Y., Lee Y.K., Hauser S.L., Crabtree-Hartman E., Sand I.K., Gacias M., Zhu Y., Casaccia P., Cree B.A.C., Knight R., Mazmanian S.K., Baranzini S.E. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA, 2017, vol. 114, no. 42: e 8943. doi: 10.1073/pnas.1716911114
  24. Chen J., Chia N., Kalari K.R., Yao J.Z., Novotna M., Soldan M.M., Luckey D.H., Marietta E.V., Jeraldo P.R., Chen X., Weinshenker B.G., Rodriguez M., Kantarci O.H., Nelson H., Murray J.A., Mangalam A.K. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci. Rep., 2016, vol. 6: 28484. doi: 10.1038/srep28484
  25. Compston A., Coles A. Multiple sclerosis. Lancet, 2008, vol. 372, no. 9648, pp. 1502–1517. doi: 10.1016/S0140-6736(08)61620-7
  26. Cosorich I., Dalla-Costa G., Sorini C., Ferrarese R., Messina M.J., Dolpady J., Radice E., Mariani A., Testoni P.A., Canducci F., Comi G., Martinelli V., Falcone M. High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci Adv., 2017, vol. 3, no. 7: e1700492. doi: 10.1126/sciadv.1700492
  27. Cua D.J., Sherlock J., Chen Y., Murphy C.A., Joyce B., Seymour B., Lucian L., To W., Kwan S., Churakova T., Zurawski S., Wiekowski M., Lira S.A., Gorman D., Kastelein R.A., Sedgwick J.D. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 2003, vol. 421, no. 6924, pp. 744–748. doi: 10.1038/nature01355
  28. Derrien M., Van Baarlen P., Hooiveld G., Norin E., Müller M., de Vos W.M. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front. Microbiol., 2011, vol. 2: 166. doi: 10.3389/ fmicb.2011.00166
  29. Derrien M., Vaughan E.E., Plugge C.M., de Vos W.M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucindegrading bacterium. Int. J. Syst. Evol. Microbiol., 2004, vol. 54, pt. 5, pp. 1469–1476. doi: 10.1099/ijs.0.02873-0
  30. Duhen T., Geiger R., Jarrossay D., Lanzavecchia A., Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat. Immunol., 2009, vol. 10, no. 8, pp. 857–863. doi: 10.1038/ni.1767
  31. Durelli L., Conti L., Clerico M., Boselli D., Contessa G., Ripellino P., Ferrero B., Eid P., Novelli F. T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta. Ann. Neurol., 2009, vol. 65, no. 5, pp. 499–509. doi: 10.1002/ ana.21652
  32. Ermolenko E., Gromova L., Borschev Yu., Voeikova A., Karaseva A., Ermolenko K., Gruzdkov A., Suvorov A. Influence of different probiotic lactic acid bacteria on microbiota and metabolism of rats with dysbiosis. Biosci. Microbiota Food Health, 2013, vol. 32, no. 2, pp. 41–49. doi: 10.12938/bmfh.32.41
  33. Fraga-Silva T.F., Mimura L.A., Marchetti C.M., Chiuso-Minicucci F., França T.G., Zorzella-Pezavento S.F., Venturini J., Arruda M.S., Sartori A. Experimental autoimmune encephalomyelitis development is aggravated by Candida albicans infection. J. Immunol. Res., 2015, 2015: 635052. doi: 10.1155/2015/635052
  34. Fylik H.A., Osborne L.C. The multibiome: the intestinal ecosystem’s influence on immune homeostasis, health, and disease. EbioMedicine, 2016, vol. 13. pp. 46–54. doi: 10.1016/j.ebiom.2016.10.007
  35. Gaboriau-Routhiau V., Rakotobe S., Lécuyer E., Mulder I., Lan A., Bridonneau C., Rochet V., Pisi A., De Paepe M., Brandi G., Eberl G., Snel J., Kelly D., Cerf-Bensussan N. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity, 2009, vol. 31, no. 4, pp. 677–689. doi: 10.1016/j.immuni.2009.08.020
  36. Ganesh B.P., Klopfleisch R., Loh G., Blaut M. Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One, 2013, vol. 8, no. 9: e74963. doi: 10.1371/journal.pone.0074963
  37. Glenn J.D., Mowry E.M. Emerging concepts on the gut microbiome and multiple sclerosis. J. Interferon Cytokine Res., 2016, vol. 36, no. 6, pp. 347–357. doi: 10.1089/jir.2015.0177
  38. Gurney A.L. IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. Int. Immunopharmacol., 2004, vol. 4, no. 5, pp. 669–677. doi: 10.1016/j.intimp.2004.01.016
  39. Hill D.A., Artis D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu. Rev. Immunol., 2010, vol. 28, pp. 623– 667. doi: 10.1146/annurev-immunol-030409-101330
  40. Ivanov I.I., Frutos Rde L., Manel N., Yoshinaga K., Rifkin D.B., Sartor R.B., Finlay B.B., Littman D.R. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe, 2008, vol. 4, no. 4, pp. 337–349. doi: 10.1016/j.chom.2008.09.009
  41. Jangi S., Gandhi R., Cox L.M., Li N., von Glehn F., Yan R., Patel B., Mazzola M.A., Liu S., Glanz B.L., Cook S., Tankou S., Stuart F., Melo K., Nejad P., Smith K., Topçuolu B.D., Holden J., Kivisäkk P., Chitnis T., De Jager P.L., Quintana F.J., Gerber G.K., Bry L., Weiner H.L. Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun., 2016, vol. 7: 12015. doi: 10.1038/ ncomms12015
  42. Kebir H., Kreymborg K., Ifergan I., Dodelet-Devillers A., Cayrol R., Bernard M., Giuliani F., Arbour N., Becher B., Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med., 2007, vol. 13, no. 10, pp. 1173–1175. doi: 10.1038/nm1651
  43. Klemann C., Raveney B.J.E., Klemann A.K., Ozawa T., von Hörsten S., Shudo K., Oki S., Yamamura T. Synthetic retinoid AM80 inhibits Th17 cells and ameliorates experimental autoimmune encephalomyelitis. Am. J. Pathol., 2009, vol. 174, no. 6, pp. 2234– 2245. doi: 10.2353/ajpath.2009.081084
  44. Korn T., Bettelli E., Gao W., Awasthi A., Jäger A., Strom T.B., Oukka M., Kuchroo V.K. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature, 2007, vol. 448, no. 7152, pp. 484–487. doi: 10.1038/nature05970
  45. Langrish C.L., Chen Y., Blumenschein W.M., Mattson J., Basham B., Sedgwick J.D., McClanahan T., Kastelein R.A., Cua D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med., 2005, vol. 201, no. 2, pp. 233– 240. doi: 10.1084/jem.20041257
  46. Lee Y.K., Menezes J.S., Umesaki Y., Mazmanian S.K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA, 2011, vol. 108, suppl. 1, pp. 4615–4622. doi: 10.1073/pnas. 1000082107
  47. Levinthal D.J., Rahman F., Nusrat S., O’Leary M., Heyman R., Bielefeldt K. Adding to the burden: gastrointestinal symptoms and syndromes in multiple sclerosis. Mult. Scler. Int., 2013, 2013: 319201. doi: 10.1155/2013/319201
  48. Liang S.C., Tan X.Y., Luxenberg D.P., Karim R., Dunussi-Joannopoulos K., Collins M., Fouser L.A. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med., 2006, vol. 203, no. 10, pp. 2271–2279. doi: 10.1084/jem.20061308
  49. Linden J.R., Ma Y., Zhao B., Harris J.M., Rumah K.R., Schaeren-Wiemers N.S., Vartanian T. Clostridium perfringens epsilon toxin causes selective death of mature oligodendrocytes and central nervous system demyelination. mBio, 2015, vol. 6, no. 3: e0513–14. doi: 10.1128/mBio.02513-14
  50. Lock C., Hermans G., Pedotti R., Brendolan A., Schadt E., Garren H., Langer-Gould A., Strober S., Cannella B., Allard J., Klonowski P., Austin A., Lad N., Kaminski N., Galli S.J., Oksenberg J.R., Raine C.S., Heller R., Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med., 2002, vol. 8, no. 5, pp. 500–508. doi: 10.1038/nm0502-500
  51. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat. Rev. Rheumatol., 2015, vol. 11, no. 10: 562. doi: 10.1038/nrrheum.2015.128
  52. Martins T.B., Rose J.W., Jaskowski T.D., Wilson A.R., Husebye D., Seraj H.S., Hill H.R. Analysis of proinflammatory and antiinflammatory cytokine serum concentrations in patients with multiple sclerosis by using a multiplexed immunoassay. Am. J. Clin. Pathol., 2011, vol. 136, no. 5, pp. 696–704. doi: 10.1309/AJCP7UBK8IBVMVNR
  53. Maynard C.L., Elson C.O., Hatton R.D., Weaver C.T. Reciprocal interactions of the intestinal microbiota and immune system. Nature, 2012, vol. 489, no. 7415, pp. 231–241. doi: 10.1038/nature11551
  54. Mazmanian S.K., Round J.L., Kasper D.L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 2008, vol. 453, no. 7195, pp. 620–625. doi: 10.1038/nature07008
  55. McFarland H.F., Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat. Immunol., 2007, vol. 8, no. 9, pp. 913– 919. doi: 10.1038/ni1507
  56. Mielcarz D.W., Kasper L.H. The gut microbiome in multiple sclerosis. Curr. Treat. Options Neurol., 2015, vol. 17, no. 4: 344. doi: 10.1007/s11940-015-0344-7
  57. Miller P.G., Bonn M.B., Franklin C.L., Ericsson A.C., McKarns S.C. TNFR2 deficiency acts in concert with gut microbiota to precipitate spontaneous sex-biased central nervous system demyelinating autoimmune disease. J. Immunol., 2015, vol. 195, no. 10, pp. 4668–4684. doi: 10.4049/jimmunol.1501664
  58. Miyake S., Kim S., Suda W., Oshima K., Nakamura M., Matsuoka T., Chihara N., Tomita A., Sato W., Kim S.W., Morita H., Hattori M., Yamamura T. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonginf to Clostridia XIVa and IV clusters. PLoS One, 2015, vol. 10, no. 9: e0137429. doi: 10.1371/journal.pone.0137429
  59. Montes M., Zhang X., Berthelot L., Laplaud D.A., Brouard S., Jin J., Rogan S., Armao D., Jewells V., Soulillou J.P., MarkovicPlese S. Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells. Clin. Immunol., 2009, vol. 130, no. 2, pp. 133–144. doi: 10.1016/j.clim.2008.08.030
  60. Mulvey M.R., Doupe M., Prout M., Leong C., Hizon R., Grossberndt A., Klowak M., Gupta A., Melanson M., Gomori A., Esfahani F., Klassen L., Frost E.E., Namaka M. Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations. Mult. Scler., 2011, vol. 17, no. 4, pp. 397–403. doi: 10.1177/1352458510391343
  61. Nibali L., Henderson B., Sadiq S.T., Donos N. Genetic dysbiosis: the role of microbial insults in chronic inflammatory diseases. J. Oral Microbiol., 2014, vol. 6: 22962. doi: 10.3402/jom.v6.22962
  62. Ochoa-Reparaz J., Mielcarz D.W., Wang Y., Begum-Haque S., Dasgupta S., Kasper D.L., Kasper L.H. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucos. Immunol., 2010, vol. 3, no. 5, pp. 487–495. doi: 10.1038/mi.2010.29
  63. Paulissen S.M., van Hamburg J.P., Dankers W., Lubberts E. The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis. Cytokine, 2015, vol. 74, no. 1, pp. 43–53. doi: 10.1016/j.cyto.2015.02.002
  64. Pickard J.M., Zeng M.Y., Caruso R., Núñez G. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol. Rev., 2017, vol. 279, no. 1, pp. 70–89. doi: 10.1111/imr.12567
  65. Pisa D., Alonso R., Jiménez-Jiménez F.J., Carrasco L. Fungal infection in cerebrospinal fluid from some patients with multiple sclerosis. Eur. J. Clin. Microbiol. Infect. Dis., 2013, vol. 32, no. 6, pp. 795–801. doi: 10.1007/s10096-012-1810-8
  66. Round J.L., Mazmanian S. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. Sci. USA, 2010, vol. 107, no. 27, pp. 12204–12209. doi: 10.1073/pnas.0909122107
  67. Rumah K.R., Linden J., Fischetti V.A., Vartanian T. Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS One, 2013, vol. 8, no. 10: e76359. doi: 10.1371/journal.pone.0076359
  68. Sallusto F., Zielinski C.E., Lanzavecchia A. Human Th17 subsets. Eur. J. Immunol., 2012, vol. 42, no. 9, pp. 2215–2220. doi: 10.1002/eji.201242741
  69. Saroukolaei S.A., Ghabaee M., Shokri H., Khosravi A., Badiei A. Evaluation of APR1 gene expression in Candida albicans strains isolated from patients with multiple sclerosis. Jundishapur. J. Microbiol., 2016, vol. 9, no. 5: e33292. doi: 10.5812/jjm.33292
  70. Scher J.U., Sczesnak A., Longman R.S., Segata N., Ubeda C., Bielski C., Rostron J.U., Cerundolo V., Pamer E.G., Abramson S.B., Huttenhower C., Littman D.R. Expansion of intestinal Prevotella copri correlates with enhance susceptibility to arthritis. Elife, 2013, vol. 2: e01202. doi: 10.7554/eLife.01202
  71. Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermúdez-Humarán L.G., Gratadoux J.J., Blugeon S., Bridonneau C., Furet J.P., Corthier G., Grangette C., Vasquez N., Pochart P., Trugnan G., Thomas G., Blottière H.M., Doré J., Marteau P., Seksik P., Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl. Acad. Sci. USA, 2008, vol. 105, no. 43, pp. 16731–16736. doi: 10.1073/pnas.0804812105
  72. Tremlett H., Fadrosh D.W., Faruqi A.A., Hart J., Roalstad S., Graves J., Spencer C.M., Lynch S.V., Zamvil S.S., Waubant E.; US Network of Pediatric MS Centers. Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurol., 2016, vol. 16, no. 1: 182. doi: 10.1186/s12883-016-0703-3
  73. Tzartos J.S., Friese M.A., Craner M.J., Palace J., Newcombe J., Esiri M.M., Fugger L. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol., 2008, vol. 172, no. 1, pp. 146–155. doi: 10.2353/ajpath.2008.070690
  74. Varrin-Doyer M., Spencer C.M., Schulze-Topphoff U., Nelson P.A., Stroud R.M., Cree B.A., Zamvil S.S. Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann. Neurol., 2012, vol. 72, no. 1, pp. 53–64. doi: 10.1002/ana.23651
  75. Wacleche V.S., Goulet J.P., Gosselin A., Monteiro P., Soudeyns H., Fromentin R., Jenabian M.A., Vartanian S., Deeks S.G., Chomont N., Routy J.P., Ancuta P. New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy. Retrovirology, 2016, vol. 13, no. 1, pp. 59. doi: 10.1186/s12977-016-0293-6
  76. Yamashita M., Ukibe K., Matsubara Y., Hosoya T., Sakai F., Kon S., Arima Y., Murakami M., Nakagawa H., Miyazaki T. Lactobacillus helveticus SBT2171 attenuates experimental autoimmune encephalomyelitis in mice. Front. Microbiol., 2018, vol. 8: 2596. doi: 10.3389/fmicb.2017.02596
  77. Zheng Y., Valdez P.A., Danilenko D.M., Hu Y., Sa S.M., Gong Q., Abbas A.R., Modrusan Z., Ghilardi N., de Sauvage F.J., Ouyang W. Interleukin-22 mediates early host defense against attaching and effacing bacterial patho, gens. Nat. Med., 2008, vol. 14, no. 3, pp. 282–289. doi: 10.1038/nm1720
  78. Zhu E., Wang X., Zheng B., Wang Q., Hao J., Chen S., Zhao Q., Zhao L., Wu Z., Yin Z. miR-20b suppresses Th17 differentiation and the pathogenesis of experimental autoimmune encephalomyelitis by targeting RORγt and STAT3. J. Immunol., 2014, vol. 192, no. 12, pp. 5599–5609. doi: 10.4049/jimmunol.1303488
  79. Zielinski C.E., Mele F., Aschenbrenner D., Jarrossay D., Ronchi F., Gattorno M., Monticelli S., Lanzavecchia A., Sallusto F. Pathogen-induced human T(H)17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature, 2012, vol. 484, no. 7395, pp. 514–518. doi: 10.1038/nature10957

Supplementary files

There are no supplementary files to display.


Copyright (c) 2019 Abdurasulova I.N., Tarasova E.A., Kudryavtsev I.V., Negoreeva I.G., Ilves A.G., Serebriakova M.K., Ermolenko E.I., Ivashkova E.V., Matsulevich A.V., Tatarinov A.E., Stoliarov I.D., Klimenko V.M., Suvorov A.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies