Functional dichotomy of dendritic cells following interaction with Leishmania braziliensis: infected cells produce high levels of TNF-alpha, whereas bystander dendritic cells are activated to promote T cell responses.
Functional dichotomy of dendritic cells following interaction with Leishmania braziliensis: infected cells produce high levels of TNF-alpha, whereas bystander dendritic cells are activated to promote T cell responses.
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DOI：
10.4049/jimmunol.181.9.6473
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发表时间：
2008-11-01
期刊：
影响因子：
--
通讯作者：
Scott P
中科院分区：
文献类型：
--
作者：
Carvalho LP;Pearce EJ;Scott P
巴西利什曼原虫感染通常与过度的免疫反应有关，有时会导致与高水平的IFN-γ和TNF-α相关的严重疾病。为了探索树突状细胞（DC）在这些反应中所起的作用，我们对暴露于L。巴西。我们发现DC在L.巴西寄生虫上调DC活化标志物并产生IL-12和TNF-α。然而，并非培养物中的所有DC都被感染，并且对感染和未感染的DC的分析表明，活化标志物和IL-12产生的上调主要限于未感染的（旁观者）DC。用transwell小室和寄生虫组分进行的进一步研究表明，旁观者DC的激活是由可溶性寄生虫产物介导的，以1型IFN和Myd 88独立但TNF-α依赖的方式，并且激活的DC比对照DC更有效地呈递抗原。与此相反，L.巴西感染的DC未能上调活化标志物，但与未感染的DC相比，它们响应于LPS产生TNF-α的能力表现出显著增强。这些发现揭示了DC在L.巴西感染：由于暴露于可溶性寄生虫产物后增强的抗原呈递能力，旁观者DC的T细胞活化，以及感染细胞产生的TNF-α增加，这可能有助于寄生虫的局部控制，但同时诱导免疫病理学。
Leishmania braziliensis infections are often associated with exaggerated immune responses that can sometimes lead to severe disease associated with high levels of IFN-γ and TNF-alpha. To explore the role played by dendritic cells (DCs) in these responses, we characterized DCs that were exposed to L. braziliensis. We found that DCs cultured with L. braziliensis parasites upregulated DC activation markers and produced IL-12 and TNF-alpha. However, not all DCs in the culture became infected, and an analysis of infected and uninfected DCs demonstrated that the upregulation of activation markers and IL-12 production was primarily confined to the uninfected (bystander) DCs. Further studies with transwell chambers and parasite fractions indicated that the activation of bystander DCs was mediated by a soluble parasite product, in a type 1 IFN and Myd88-independent but TNF-alpha-dependent fashion, and that the activated DCs were more efficient at presenting antigen than control DCs. In contrast, L. braziliensis infected DCs failed to upregulate activation markers, but exhibited a dramatic enhancement in their ability to produce TNF-alpha in response to LPS as compared to uninfected DCs. These findings uncover a dual role for DCs in L. braziliensis infection: T cell activation by bystander DCs due to enhanced antigen presenting capacity following exposure to soluble parasite products, and increased production of TNF-alpha by infected cells that may contribute to the local control of the parasites but concomitantly induce immunopathology.
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I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
2.8
作者：
DaCruz, AM;deOliveira, MP;Coutinho, SG
通讯作者：
Coutinho, SG
影响因子：
4.6
作者：
ETTEHADI, P;GREAVES, MW;CAMP, RDR
通讯作者：
CAMP, RDR
影响因子：
2.4
作者：
ILG, T;STIERHOF, YD;OVERATH, P
通讯作者：
OVERATH, P
影响因子：
5.4
作者：
KAYE, PM;ROGERS, NJ;SCOTT, JC
通讯作者：
SCOTT, JC