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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The porin OmpD from nontyphoidal Salmonella is a key target for a protective B1b cell antibody response
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The porin OmpD from nontyphoidal Salmonella is a key target for a protective B1b cell antibody response

机译：非伤寒沙门氏菌的孔蛋白OmpD是保护性B1b细胞抗体反应的关键靶标

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摘要

Invasive nontyphoidal Salmonella (NTS), including Salmonella typhi-murium (STm), are major yet poorly-recognized killers of infants in sub-Saharan Africa. Death in these children is usually associated with bacteremia, commonly in the absence of gastrointestinal symptoms. Evidence from humans and animal studies suggest that severe infection and bacteremia occur when specific Ab is lacking. Understanding how Ab responses to Salmonella are regulated will help develop vaccines against these devastating infections. STm induces atypical Ab responses characterized by prominent, accelerated, extrafollicular T-independent (Tl) Ab against a range of surface antigens. These responses develop without concomitant germinal centers, which only appear as infection resolves. Here, we show STm rapidly induces a population of Tl B220~+ CD5~- B1 b cells during infection and Tl Ab from B1b cells targets the outer membrane protein (Omp) porins OmpC, OmpD and OmpF but not flagellin. When porins are used as immu-nogens they can ablate bacteremia and provide equivalent protection against STm as killed bacterial vaccine and this is wholly B cell-dependent. Furthermore Ab from porin-immunized chimeras, that have B1b cells, is sufficient to impair infection. Infecting with porin-deficient bacteria identifies OmpD, a protein absent from Salmonella Typhi, as a key target of Ab in these infections. This work broadens the recognized repertoire of Tl protein antigens and highlights the importance of Ab from different B cell subsets in controlling STm infection. OmpD is a strong candidate vaccine target and may, in part, explain the lack of cross-protection between Salmonella Typhi and STm infections.
机译：包括伤寒沙门氏菌（STm）在内的非伤寒沙门氏菌（NTS）是撒哈拉以南非洲地区主要但尚未得到公认的婴儿杀手。这些儿童的死亡通常与菌血症有关，通常没有胃肠道症状。人类和动物研究的证据表明，当缺乏特定的抗体时，会发生严重的感染和菌血症。了解Ab对沙门氏菌反应的调控方式将有助于开发针对这些破坏性感染的疫苗。 STm诱导非典型的Ab反应，其特征是针对一系列表面抗原的突出，加速，滤泡外T独立（Tl）Ab。这些反应在没有生发中心的情况下发展，仅在感染消退时出现。在这里，我们显示STm在感染过程中迅速诱导了T1 B220〜+ CD5〜-B1b细胞的聚集，来自B1b细胞的T1 Ab靶向外膜蛋白（Omp）孔蛋白OmpC，OmpD和OmpF，但不是鞭毛蛋白。当孔蛋白用作免疫原时，它们可以消除菌血症，并提供与杀灭的细菌疫苗相同的针对STm的保护，这完全依赖于B细胞。此外，具有B1b细胞的孔蛋白免疫嵌合体的Ab足以削弱感染。用缺乏孔蛋白的细菌感染可以将伤寒沙门氏菌缺少的蛋白OmpD鉴定为这些感染中Ab的主要靶标。这项工作拓宽了公认的T1蛋白抗原库，并强调了来自不同B细胞亚群的Ab在​​控制STm感染中的重要性。 OmpD是一个很强的候选疫苗目标，可能部分解释了伤寒沙门氏菌和STm感染之间缺乏交叉保护。

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    Cristina Gil-Cruz; Saeeda Bobat; Jennifer L. Marshall; Robert A. Kingsley; Ewan A. Ross; Ian R. Henderson; Denisse L. Leyton; Ruth E. Coughlan; Mahmood Khan; Karina T. Jensen; Christopher D. Buckley; Gordon Dougan; Ian C. M. MacLennan; Constantino Lopez-Macias; Adam F. Cunningham;

  • 作者单位

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI' Mexican Institute for Social Security, Mexico City, Mexico Program on Immunology, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

    Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI' Mexican Institute for Social Security, Mexico City, Mexico;

    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    B cells; vaccines;

    机译：B细胞;疫苗;

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