Functional impairment of human myeloid dendritic cells during Schistosoma haematobium infection.
Functional impairment of human myeloid dendritic cells during Schistosoma haematobium infection.
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DOI：
10.1371/journal.pntd.0000667
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发表时间：
2010-04-20
影响因子：
3.8
通讯作者：
Yazdanbakhsh M
中科院分区：
文献类型：
--
作者：
Everts B;Adegnika AA;Kruize YC;Smits HH;Kremsner PG;Yazdanbakhsh M
慢性血吸虫感染的特征通常是宿主的T细胞低反应性状态。树突状细胞（DC）功能的抑制可能是这种现象背后的机制之一，因为血吸虫抗原是体外树突状细胞功能的有效调节剂。然而，它仍然有待确定是否DC功能在体内慢性人血吸虫感染过程中调制。为了解决这个问题，埃及血吸虫感染对人血DC功能的影响进行了评估。我们发现，浆细胞样（pDC）和髓样DC（mDC）从感染的受试者是目前在外周血中的频率较低，并显示较低的HLA-DR的表达水平相比，从未感染的个人。此外，发现来自感染受试者的mDC而不是pDC具有降低的响应TLR配体的能力，如通过MAPK信号传导、细胞因子产生和成熟标志物的表达所确定的。此外，来自感染受试者的TLR成熟mDC的T细胞活化能力较低，可能是由于HLA-DR表达减少。这些数据表明S.血吸虫感染与体内人DC功能的功能损害有关，并为慢性血吸虫病期间T细胞低反应性的潜在机制提供了新的见解。血吸虫病以及其他系统性蠕虫感染的一个关键特征是其慢性性质。这反映了寄生虫成功逃避和抑制宿主免疫反应。这种现象背后的机制之一是树突状细胞（DC）的调节，树突状细胞在T细胞应答的启动和控制中起着核心作用。尽管一些体外研究已经证明了血吸虫抗原对DC功能的调节能力，但血吸虫病对体内人DC功能的影响仍不清楚。为了解决这个问题，我们从生活在非洲中部血吸虫病流行区的感染和未感染个体的外周血中分离出两个主要的DC亚群，并发现特别是血吸虫感染受试者的髓样DC显示出对Toll样受体配体应答和驱动T细胞应答的能力受损。这些发现为血吸虫病如何抑制宿主免疫反应提供了新的见解，这可以用于新的策略来增强对寄生虫的免疫力。
Chronic Schistosoma infection is often characterized by a state of T cell hyporesponsiveness of the host. Suppression of dendritic cell (DC) function could be one of the mechanisms underlying this phenomenon, since Schistosoma antigens are potent modulators of dendritic cell function in vitro. Yet, it remains to be established whether DC function is modulated during chronic human Schistosoma infection in vivo. To address this question, the effect of Schistosoma haematobium infection on the function of human blood DC was evaluated. We found that plasmacytoid (pDC) and myeloid DC (mDC) from infected subjects were present at lower frequencies in peripheral blood and that mDC displayed lower expression levels of HLA-DR compared to those from uninfected individuals. Furthermore, mDC from infected subjects, but not pDC, were found to have a reduced capacity to respond to TLR ligands, as determined by MAPK signaling, cytokine production and expression of maturation markers. Moreover, the T cell activating capacity of TLR-matured mDC from infected subjects was lower, likely as a result of reduced HLA-DR expression. Collectively these data show that S. haematobium infection is associated with functional impairment of human DC function in vivo and provide new insights into the underlying mechanisms of T cell hyporesponsiveness during chronic schistosomiasis. A key feature of schistosomiasis, as well as of other systemic helminth infections, is their chronic nature. This reflects the successful evasion and suppression of host immune responses by the parasites. One of the mechanisms that could underlie this phenomenon is modulation of the dendritic cells (DC), which play a central role in initiation and control of T cell responses. Although several in vitro studies have documented the modulatory capacity of Schistosoma antigens on DC function, it is still unclear what effect schistosomiasis has on human DC function in vivo. To address this question, we isolated the two main DC subsets present in peripheral blood from infected and uninfected individuals living in a Schistosoma-endemic area in central Africa, and found that specifically the myeloid DC from Schistosoma-infected subjects displayed an impaired capacity to respond to Toll-like receptor ligands and to drive T cell responses. These findings provide new insights into how schistosomiasis suppresses host immune responses, which can be exploited for new strategies to enhance immunity against the parasites.
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影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
DOI：
10.1111/j.1440-1746.2004.03529.x
发表时间：
2005-02-01
影响因子：
4.1
作者：
Duan, XZ;Zhuang, H;Wang, FS
通讯作者：
Wang, FS
影响因子：
4.4
作者：
Kane, CM;Cervi, L;Pearce, EJ
通讯作者：
Pearce, EJ
影响因子：
4.4
作者：
Arrighi, JF;Rebsamen, M;Hauser, C
通讯作者：
Hauser, C