Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus

Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus
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DOI:
10.4049/jimmunol.177.9.5861
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发表时间:
2006-11-01
影响因子:
4.4
通讯作者:
Holt, Patrick G.
Holt, Patrick G.
中科院分区:
医学2区
文献类型:
--
作者:
Jahnsen, Frode L.;Strickland, Deborah H.;Holt, Patrick G.

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局部树突状细胞(DC)介导的免疫监视的克里思的增加是气道粘膜表面对急性炎症的应答的公认特征,并且这些DC在迁移到区域淋巴结之前的APC功能的瞬时上调最近已被确定为在疾病如哮喘中T细胞介导的气道组织损伤的重要触发因素。在这项研究中,使用大鼠模型,我们证明了气道粘膜DC(AMDC)的动力学响应的挑战与热灭活细菌是相当快的,因此更有效地划分比回忆响应可溶性Ag。值得注意的是,携带Ag的AMDC表达完整的APC活性在停止微生物暴露后30分钟内到达区域淋巴结,并且与对非致病性Ag的回忆反应相反,没有证据表明DC迁移前气道粘膜内APC活性的局部表达。我们还证明,类似于在肠道中报道的,气道上皮内DC的一个子集将其过程延伸到气道腔中。这种功能在AMDC群体中组成型表达,提供了在没有“危险”信号的情况下持续免疫监视气道腔表面的机制。
An increase in the tempo of local dendritic cell (DC)-mediated immune surveillance is a recognized feature of the response to acute inflammation at airway mucosal surfaces, and transient up-regulation of the APC functions of these DC preceding their emigration to regional lymph nodes has recently been identified as an important trigger for T cell-mediated airway tissue damage in diseases such as asthma. In this study, using a rat model, we demonstrate that the kinetics of the airway mucosal DC (AMDC) response to challenge with heat-killed bacteria is considerably more rapid and as a consequence more effectively compartmentalized than that in recall responses to soluble Ag. Notably, Ag-bearing AMDC expressing full APC activity reach regional lymph nodes within 30 min of cessation of microbial exposure, and in contrast to recall responses to nonpathogenic Ags, there is no evidence of local expression of APC activity within the airway mucosa preceding DC emigration. We additionally demonstrate that, analogous to that reported in the gut, a subset of airway intraepithelial DC extend their processes into the airway lumen. This function is constitutively expressed within the AMDC population, providing a mechanism for continuous immune surveillance of the airway luminal surface in the absence of "danger", signals.