Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells

被引:187
作者
Bermejo, Daniela A. [1 ]
Jackson, Shaun W. [2 ,3 ]
Gorosito-Serran, Melisa [1 ]
Acosta-Rodriguez, Eva V. [1 ]
Amezcua-Vesely, Maria C. [1 ]
Sather, Blythe D. [2 ,3 ]
Singh, Akhilesh K. [2 ,3 ]
Khim, Socheath [2 ,3 ]
Mucci, Juan [4 ]
Liggitt, Denny [5 ]
Campetella, Oscar [4 ]
Oukka, Mohamed [2 ,3 ,6 ]
Gruppi, Adriana [1 ]
Rawlings, David J. [2 ,3 ,6 ]
机构
[1] Univ Nacl Cordoba, Consejo Nacl Invest Cient & Tecn, Fac Ciencias Quim, Ctr Invest Bioquim Clin & Inmunol, RA-5000 Cordoba, Argentina
[2] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA
[3] Seattle Childrens Res Inst, Seattle, WA USA
[4] Univ Nacl San Martin, Inst Invest Biotecnol, San Martin, Argentina
[5] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA
[6] Univ Washington, Sch Med, Dept Immunol, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
CAMPYLOBACTER-JEJUNI; RECEPTOR; INFECTION; ANTIGEN; DIFFERENTIATION; EXPRESSION; IMMUNITY; SIALYLTRANSFERASE; IDENTIFICATION; GLYCOSYLATION;
D O I
10.1038/ni.2569
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Here we identified B cells as a major source of rapid, innate-like production of interleukin 17 (IL-17) in vivo in response to infection with Trypanosoma cruzi. IL-17(+) B cells had a plasmablast phenotype, outnumbered cells of the T(H)17 subset of helper T cells and were required for an optimal response to this pathogen. With both mouse and human primary B cells, we found that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell-surface mucin CD45, which led to signaling dependent on the kinase Btk and production of IL-17A or IL-17F via a transcriptional program independent of the transcription factors ROR gamma t and Ahr. Our combined data suggest that the generation of IL-17(+) B cells may be a previously unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.
引用
收藏
页码:514 / +
页数:11
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