A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease

被引:393
作者
Ochoa-Reparaz, J. [1 ]
Mielcarz, D. W. [2 ]
Wang, Y. [2 ]
Begum-Haque, S. [1 ]
Dasgupta, S. [3 ,4 ]
Kasper, D. L. [3 ,4 ]
Kasper, L. H. [1 ]
机构
[1] Dartmouth Med Sch, Dept Med & Neurol, Lebanon, NH USA
[2] Dartmouth Med Sch, Dept Microbiol Immunol, Lebanon, NH USA
[3] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DENDRITIC CELL SUBSETS; INTERFERON-GAMMA; T-CELLS; DEFICIENT MICE; INDUCTION; IL-10; SUPPRESSION; POPULATION;
D O I
10.1038/mi.2010.29
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The intestinal microbiome may have a critical roll in susceptibility or resistance to immune-mediated diseases. Alterations of the gut microflora after oral antibiotic treatment can regulate encephalomyelitis (EAE), an animal model for human multiple sclerosis (MS). We now show that a zwitterionic capsular polysaccharide A (PSA) of Bacteroides fragilis can protect against central nervous system demyelinating disease. Oral administration with purified PSA protected mice against EAE prophylactic and therapeutically. PSA treatment enhanced CD103 expressing dendritic cells (DCs) that accumulated in the cervical lymph nodes. Exposure of naive DCs to PSA induced the conversion of naive CD4(+) T cells into interleukin (IL)-10-producing FoxP3(+) Treg cells. Protection against EAE was completely abrogated in IL-10-deficient mice. Our results show an important role for a molecule from human commensal bacteria in protecting against EAE and suggest the possibility for protection in MS.
引用
收藏
页码:487 / 495
页数:9
相关论文
共 38 条
[11]  
Ferber IA, 1996, J IMMUNOL, V156, P5
[12]   Induction of low dose oral tolerance in IL-10 deficient mice with experimental autoimmune encephalomyelitis [J].
Gonnella, PA ;
Waldner, HP ;
Kodali, D ;
Weiner, HL .
JOURNAL OF AUTOIMMUNITY, 2004, 23 (03) :193-200
[13]   Differential response of respiratory dendritic cell subsets to influenza virus infection [J].
Hao, Xueli ;
Kim, Taeg S. ;
Braciale, Thomas J. .
JOURNAL OF VIROLOGY, 2008, 82 (10) :4908-4919
[14]   Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J].
Harrington, LE ;
Hatton, RD ;
Mangan, PR ;
Turner, H ;
Murphy, TL ;
Murphy, KM ;
Weaver, CT .
NATURE IMMUNOLOGY, 2005, 6 (11) :1123-1132
[15]   Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis [J].
Hofstetter, HH ;
Ibrahim, SM ;
Koczan, D ;
Kruse, N ;
Weishaupt, A ;
Toyka, KV ;
Gold, R .
CELLULAR IMMUNOLOGY, 2005, 237 (02) :123-130
[16]  
Karpus WJ, 1998, J IMMUNOL, V161, P2667
[17]   Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses [J].
Kim, Taeg S. ;
Braciale, Thomas J. .
PLOS ONE, 2009, 4 (01)
[18]   Hygiene hypothesis in inflammatory bowel disease: A critical review of the literature [J].
Koloski, Natasha A. ;
Bret, Laurel ;
Radford-Smith, Graham .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (02) :165-173
[19]   IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].
Komiyama, Yutaka ;
Nakae, Susumu ;
Matsuki, Taizo ;
Nambu, Aya ;
Ishigame, Harumichi ;
Kakuta, Shigeru ;
Sudo, Katsuko ;
Iwakura, Yoichiro .
JOURNAL OF IMMUNOLOGY, 2006, 177 (01) :566-573
[20]   A Novel Probiotic Mixture Exerts a Therapeutic Effect on Experimental Autoimmune Encephalomyelitis Mediated by IL-10 Producing Regulatory T Cells [J].
Lavasani, Shahram ;
Dzhambazov, Balik ;
Nouri, Mehrnaz ;
Fak, Frida ;
Buske, Sophia ;
Molin, Goran ;
Thorlacius, Henrik ;
Alenfall, Jan ;
Jeppsson, Bengt ;
Westrom, Bjorn .
PLOS ONE, 2010, 5 (02)