Mycobacterium bovis BCG-mediated suppression of Th17 response in mouse experimental autoimmune encephalomyelitis.

Autor: Matsuzaki G; Molecular Microbiology Group, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Japan.; Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan., Teruya N; Molecular Microbiology Group, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Japan., Kiyohara Kohama H; Research and Development Department, Japan BCG Laboratory, Kiyose, Japan., Arai K; Research and Development Department, Japan BCG Laboratory, Kiyose, Japan., Shibuya Y; Research and Development Department, Japan BCG Laboratory, Kiyose, Japan., Chuma Y; Research and Development Department, Japan BCG Laboratory, Kiyose, Japan., Matsuo K; Research and Development Department, Japan BCG Laboratory, Kiyose, Japan.
Jazyk: angličtina
Zdroj: Immunopharmacology and immunotoxicology [Immunopharmacol Immunotoxicol] 2021 Apr; Vol. 43 (2), pp. 203-211. Date of Electronic Publication: 2021 Feb 04.
DOI: 10.1080/08923973.2021.1878215
Abstrakt: Introduction: Multiple sclerosis (MS) is an autoimmune disease mediated by a pro-inflammatory immune response. Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice with a myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in killed Mycobacterium tuberculosis -containing complete Freund's adjuvant (CFA-EAE) is used as a model of MS. Mycobacterium bovis BCG has been reported to ameliorate clinical symptoms of CFA-EAE, although the precise mechanism has not yet been documented. Since CFA-EAE uses adjuvant with mycobacterial antigens, mycobacterial antigen-specific T cells induced by CFA may cross-react with BCG and modulate EAE.
Methods: To exclude the influence of cross-reactivity, a modified murine EAE model (cell wall skeleton (CWS)-EAE) that does not induce mycobacterial antigen-specific T cells was established and used to reevaluate the therapeutic effects of BCG on EAE.
Results: Inoculation with BCG 6 d after CWS-EAE induction successfully ameliorated EAE symptoms, suggesting that the therapeutic effects of BCG are independent of the mycobacterial antigen-specific T cells induced by the CFA-EAE protocol. BCG inoculation into the CWS-EAE mice resulted in reduced levels of MOG-specific Th17 in the central nervous system (CNS) with reduced demyelinated lesions of the spinal cord. In the draining lymph nodes of the MOG-immunized sites, BCG inoculation resulted in an increase in MOG-specific Th17 and Th1 cells at an early stage of immune response.
Conclusion: The results suggest that BCG inoculation suppresses the Th17 response in the CNS of EAE mice via a mechanism that may involve the suppression of egress of encephalitogenic T cells from lymphoid organs.
Databáze: MEDLINE
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