Impact of Leishmania mexicana infection on dendritic cell signaling and functions.
Impact of Leishmania mexicana infection on dendritic cell signaling and functions.
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墨西哥利什曼病感染对树突状细胞信号传导和功能的影响
DOI：
10.1371/journal.pntd.0003202
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Olivier M
中科院分区：
文献类型：
--
作者：
Contreras I;Estrada JA;Guak H;Martel C;Borjian A;Ralph B;Shio MT;Fournier S;Krawczyk CM;Olivier M
利什曼原虫具有改变巨噬细胞信号通路的能力，以便在其哺乳动物宿主内生存和繁殖。它们也侵入其他细胞，包括中性粒细胞、成纤维细胞和树突状细胞（dc）。dc作为先天免疫和适应性免疫之间的纽带，在免疫中发挥着重要作用，是形成有效应答的必要条件；然而，墨西哥利什曼原虫感染对dc的影响研究甚少。本文报道，利什曼原虫感染可迅速诱导DC蛋白酪氨酸磷酸酶活性，导致MAP激酶失活。与此相一致的是，墨西哥L.可以减少AP-1和NF-κB等转录因子的核易位。同时，L. mexicana感染的dc在LPS刺激下表现出几种表面抗原呈递和共刺激分子的表达降低。利什曼原虫对DC成熟的干扰进一步体现在它们向OVA特异性T细胞呈递OVA抗原的能力降低，这表明T细胞不再产生IL-2。总的来说，我们的数据显示，墨西哥乳杆菌感染DC似乎影响了有效和保护性免疫反应发展所必需的细胞和免疫机制，因此有利于寄生虫在其宿主内的生存和繁殖。利什曼原虫属的寄生虫已经发展出许多在宿主体内生存的策略。最初，它们只被认为能够感染巨噬细胞；然而，已经观察到利什曼原虫能够感染其他类型的细胞，如成纤维细胞、中性粒细胞和树突状细胞（dc）。dc以其抗原呈递能力而闻名，它们被认为是先天免疫反应和适应性免疫反应之间的基本桥梁。在本研究中，我们试图阐明墨西哥L. promastigotes对DCs的影响。我们的研究结果表明，L. mexicana灭活了负责免疫效应分子（如细胞因子）表达的信号级联，伴随着宿主蛋白磷酸酶的激活。此外，我们观察到，promastigote感染的细胞表面MHC和共刺激分子的表达较低，抗原呈递能力也下降。总之，我们的研究表明利什曼原虫能够灭活dc的免疫机制，就像它们在巨噬细胞中一样，以便在宿主体内存活。
Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs). DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied. Herein, we report that Leishmania infection rapidly induced DC protein tyrosine phosphatases activity, leading to MAP kinases inactivation. In line with this, L. mexicana was found to decrease the nuclear translocation of transcription factors such as AP-1 and NF-κB. Concomitantly, L. mexicana-infected DCs showed reduced expression of several surface antigen-presenting and co-stimulatory molecules upon LPS stimulation. Leishmania-induced interference on DC maturation was further reflected by their reduced capacity to present OVA antigen to OVA-specific T cells, as shown by abrogation of IL-2 production by the T cells. Collectively, our data revealed that DC infection by L. mexicana appears to affect the cellular and immunological mechanisms necessary for the development of an effective and protective immune response, therefore favouring the survival and propagation of the parasite within its host. Parasites of the Leishmania genus have developed many strategies to survive inside their host. Initially, they were only considered capable of infecting macrophages; however, it has been observed that Leishmania is able to infect other cell types, such as fibroblast, neutrophils and dendritic cells (DCs). DCs are well known for their antigen-presentation capabilities, and they are considered as the fundamental bridge between the innate and adaptive immune responses. In this study, we attempted to elucidate the effect of L. mexicana promastigotes on DCs. Our results showed that L. mexicana inactivates signaling cascades responsible for the expression of immune effector molecules, such as cytokines, concomitantly with the activation of protein phosphatases in the host. Furthermore, we observed that promastigote-infected cells had lower expression of MHC and co-stimulatory molecules on their surface, as well as decreased antigen-presentation capacity. In conclusion, our study showed that Leishmania parasites are able to inactivate the immunological mechanisms of DCs, as they do in macrophages, in order to survive inside its host.
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影响因子：
6.7
作者：
Contreras I;Gómez MA;Nguyen O;Shio MT;McMaster RW;Olivier M
通讯作者：
Olivier M
DOI：
10.1084/jem.191.12.2121
发表时间：
2000-06-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bogdan C;Donhauser N;Döring R;Röllinghoff M;Diefenbach A;Rittig MG
通讯作者：
Rittig MG
影响因子：
4.4
作者：
Jaramillo, M;Olivier, M
通讯作者：
Olivier, M
影响因子：
3.1
作者：
Liu, Dong;Kebaier, Chahnaz;Uzonna, Jude E.
通讯作者：
Uzonna, Jude E.
影响因子：
15.3
作者：
Kima, PE;Constant, SL;McMahon-Pratt, D
通讯作者：
McMahon-Pratt, D