Dendritic cells play a role in host susceptibility to Cryptosporidium parvum infection
Dendritic cells play a role in host susceptibility to Cryptosporidium parvum infection
复制标题
DOI：
10.1016/j.imlet.2013.11.015
复制
发表时间：
2014-03-01
影响因子：
4.4
通讯作者：
Mead, Jan R.
中科院分区：
文献类型：
--
作者：
Bedi, Brahmchetna;McNair, Nina N.;Mead, Jan R.
我们以前的研究已经描述了树突状细胞（DC）的重要来源的Th 1细胞因子，如IL-12和IL-2在体外，与隐孢子虫抗原刺激后。我们使用白喉毒素启动子调节的转基因CD 11 c-DTR/EGFP小鼠模型进一步建立了DCs在隐孢子虫病中的作用。在CD 11 c-DTR-Tg小鼠中，体内去除CD 11 c（+）细胞显著增加了对微小隐孢子虫感染的易感性。将未刺激或抗原刺激的DC连续转移到CD 11 c（+）耗尽的CD 11 c-DTR-Tg小鼠中导致感染后4天寄生虫负荷的早期降低。然而，这种反应是短暂的，因为在感染后6天，用未刺激的DC或用溶解的抗原刺激的DC移植的小鼠中寄生虫负荷增加。相比之下，在用活子孢子刺激的DC移植的小鼠中，寄生虫负荷在整个期间保持较低，表明产生了更有效和持续的应答。还注意到来自脾和肠系膜淋巴结的T细胞中IFN-γ表达的相应增加。与体内植入研究一致，体外用活子孢子脉冲并与CD 4（+）和CD 8（+）T细胞共培养的DC产生更高的IFN-γ水平。我们的研究确立了DC在小隐孢子虫感染易感性中的重要性，并作为免疫应答的重要介质。由爱思唯尔公司出版
Our previous studies have described dendritic cells (DCs) to be important sources of Th1 cytokines such as IL-12 and IL-2 in vitro, following stimulation with Cryptosporidium parvum antigens. We further established the role of DCs during cyptosporidiosis using a diphtheria toxin promoter regulated transgenic CD11c-DTR/EGFP mouse model. In vivo depletion of CD11c(+) cells in CD11c-DTR-Tg mice significantly increased susceptibility to C parvum infection. Adoptive transfer of unstimulated or antigen stimulated DCs into CD11c(+) depleted CD11c-DTR-Tg mice resulted in an early decrease in parasite load at 4 days post infection. However, this response was transient since parasite load increased in mice engrafted with either unstimulated DCs or DCs stimulated with solubilized antigen by 6 days post infection. In contrast, in mice engrafted with DCs stimulated with live sporozoites, parasite load remained low during the entire period, suggesting the development of a more effective and sustained response. A corresponding increase in IFN-gamma expression in T cells from spleen and mesenteric lymph nodes was also noted. Consistent with the in vivo engraftment study, DCs that are pulsed with live sporozoites in vitro and co-cultured with CD4(+) and CD8(+) T cells produced higher IFN-gamma levels. Our study establishes the importance of DCs in susceptibility to infection by C parvum and as important mediators of immune responses. Published by Elsevier B.V.