Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania major:: inverse relationship to interleukin-12 production

Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania major:: inverse relationship to interleukin-12 production
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DOI:
10.1128/iai.70.7.3874-3880.2002
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发表时间:
2002-07-01
影响因子:
3.1
通讯作者:
Handman, E
Handman, E
中科院分区:
医学2区
文献类型:
--
作者:
Henri, S;Curtis, J;Handman, E

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树突状细胞(DC)是启动和调节T细胞免疫反应的专职抗原提呈细胞。在这里,我们表明,小鼠脾DC可以根据其吞噬和庇护主要细胞内寄生虫利什曼原虫的能力进行排名。CD_4~(+)、CD_8~(-)、CD_4~(-)、CD_8~(+)、CD_4~(-)、CD_8~(+)、CD_4~(-)、CD_8~(-)、CD_4~(+)、CD_4~(-)、CD_8~(-)、CD_4~+、CD_4~+、CD_8~+、CD_4~+、CD_4~+、CD_然而,最不敏感的CD4(-)CD8(+)DC亚群是最好的白介素12产生者。感染不会诱导任何DC亚群产生与诱导Th1反应相关的促炎细胞因子γ-干扰素和一氧化氮。树突状细胞吞噬的寄生虫数量很少,每个细胞不超过3个微生物,而每个巨噬细胞超过10个微生物。在感染的DC中,寄生虫位于含有主要组织相容性复合体(MHC)II类和溶酶体相关的膜蛋白I分子的寄生空泡中,与它们在感染的巨噬细胞中的位置相似。寄生虫驱动的MHC II类分子重新分布到这个隔室,表明受感染的DC应该能够呈递寄生虫抗原。
Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4(+) CD8(-) DCs are the most permissive host cells for L. major amastigotes, followed by CD4(-) CD8(-) DCs; CD4(-) CD8(+) cells are the least permissive. However, the least susceptible CD4(-) CD8(+) DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein I molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.