Sialylation of Campylobacter jejuni Endotoxin Promotes Dendritic Cell-Mediated B Cell Responses through CD14-Dependent Production of IFN-β and TNF-α
Sialylation of Campylobacter jejuni Endotoxin Promotes Dendritic Cell-Mediated B Cell Responses through CD14-Dependent Production of IFN-β and TNF-α
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DOI：
10.4049/jimmunol.1301536
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Jacobs, Bart C.
中科院分区：
文献类型：
--
作者：
Huizinga, Ruth;van Rijs, Wouter;Jacobs, Bart C.
空肠弯曲菌是人类胃肠炎最常见的细菌性病因，并且通常先于格林-巴利综合征（GBS）的发展，GBS是一种危及生命的麻痹性疾病。糖唾液酸掺入C。空肠脂寡糖（LOS）与胃肠炎严重程度增加和GBS诱导有关;然而，其潜在机制仍完全未知。在这项研究中，我们证明了唾液酸在C。空肠内毒素增强人树突状细胞（DC）快速产生IFN-β和TNF-α。使用中和Ab和受体，显示这些DC衍生的细胞因子以不依赖于T细胞的方式促进人粘膜B细胞的增殖。DCs对LOS的应答产生IFN-β和TNF-α需要CD 14，而DCs对唾液酸化的C.空肠LOS是CD 14依赖性的。总之，这些结果表明C.空肠LOS通过CD 14驱动的IFN-β和TNF-α的产生增加DC活化并促进随后的B细胞应答。这种增强的DC/B细胞反应可以解释唾液酸化C的致病性增加。可能是GBS中B细胞介导的自身免疫启动的关键。
Campylobacter jejuni is the most common bacterial cause of human gastroenteritis and often precedes development of Guillain-Barre syndrome (GBS), a life-threatening paralytic disease. The incorporation of the carbohydrate sialic acid into C. jejuni lipooligosaccharides (LOS) is associated with increased severity of gastroenteritis and with induction of GBS; however, the underlying mechanisms remain completely unknown. In this study, we demonstrate that sialic acids in C. jejuni endotoxin enhance the rapid production of IFN-beta and TNF-alpha by human dendritic cells (DCs). Using neutralizing Abs and receptors it was shown that these DC-derived cytokines promote the proliferation of human mucosal B cells in a T cell-independent manner. The production of both IFN-beta and TNF-alpha by DCs in response to LOS requires CD14, and the amplified response of DCs to sialylated C. jejuni LOS is CD14 dependent. Together, these results indicate that sialylation of C. jejuni LOS increases DC activation and promotes subsequent B cell responses through CD14-driven production of IFN-beta and TNF-alpha. This enhanced DC/B cell response may explain the increased pathogenicity of sialylated C. jejuni and may be key to the initiation of B cell-mediated autoimmunity in GBS.