Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice
Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice
复制标题
DOI：
10.1128/iai.01217-06
复制
发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Snapper, Clifford M.
中科院分区：
文献类型：
--
作者：
Colino, Jesus;Snapper, Clifford M.
在体内，外切体可以激活T细胞，但外切体是否能够诱导体液免疫反应尚不清楚。我们发现，树突状细胞，而不是其他免疫细胞，结构性地释放一种与肺炎链球菌14型被膜多糖(CPSM-CRA)交叉反应的外体相关糖偶联物。Cps14-CRA定位于外切体富含胆固醇的微区或筏，并定位于Cps14-CRA的β1-GT；6支化N-乙酰乳糖胺衍生物。将纯化的树突状细胞外体注射CFA免疫幼鼠，可诱导免疫球蛋白(Ig)产生主要由IgM、IgG3和IgG1组成的抗Cps14反应。这些反应与抵抗14型肺炎链球菌的致死攻击有关，但与3型细菌无关，并与诱导的IgM和IgG3抗Cps14抗体的滴度相关。这些数据首次表明，外切体可以诱导对相关的未经处理的自体抗原的体液免疫反应。虽然抗Cps14免疫球蛋白的反应是专门证明的，但这些反应可能反映了一种更广泛的机制，既调节了自然免疫，也调节了对其他糖链的自身免疫。
Exosomes activate T cells in vivo, but whether exosomes are able to induce humoral immune responses is still unknown. We found that dendritic cells, but not other immune cells, constitutively release an exosome-associated glycoconjugate that is cross-reactive with the capsular polysaccharide of Streptococcus pneumoniae type 14 (CpsM-CRA). Cps14-CRA was localized to the cholesterol-enriched microdomains or rafts of the exosomes and was mapped to the beta 1 -> 6 branched N-acetyl-lactosamine derivatives of the Cps14-CRA. Injection of CFA-primed naive mice with purified dendritic cell exosomes induced immunoglobulin (Ig) anti-Cps14 responses composed predominantly of IgM, IgG3, and IgG1. These responses were associated with protection against a lethal challenge with live S. pneumoniae type 14, but not with type 3 bacteria, and was correlated with the titer of elicited IgM and IgG3 anti-Cps14. These data show, for the first time, that exosomes can induce a humoral immune response to an associated unprocessed, autologous antigen. Although anti-Cps14 Ig responses are specifically demonstrated, these could reflect a broader mechanism that modulates both natural immunity and autoimmunity to other glycotopes.