Conventional CD11c(high) Dendritic Cells Are Important for T Cell Priming during the Initial Phase of Plasmodium yoelii Infection, but Are Dispensable at Later Time Points.
Conventional CD11c(high) Dendritic Cells Are Important for T Cell Priming during the Initial Phase of Plasmodium yoelii Infection, but Are Dispensable at Later Time Points.
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DOI：
10.3389/fimmu.2017.01333
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发表时间：
2017
影响因子：
7.3
通讯作者：
Hansen W
中科院分区：
文献类型：
--
作者：
Ueffing K;Abberger H;Westendorf AM;Matuschewski K;Buer J;Hansen W
树突状细胞（Dendritic cells，DC）是高度特化的抗原呈递细胞，其协调针对病原体的适应性免疫应答。在疟疾感染期间，促炎性和抗炎性T细胞应答必须紧密平衡，以确保寄生虫清除而不诱导严重的免疫病理。然而，CD 11 chigh DCs在这一过程中的确切作用仍存在争议。在这里，我们证明了在约氏疟原虫（约氏疟原虫）感染的白喉毒素（DT）治疗的RosaiDTR/CD 11 c-cre小鼠中，常规CD 11 chigh DCs的长期耗竭干扰了感染早期CD 8+和CD 4 + T细胞以及CD 4 + Foxp 3+调节性T细胞的活化。此外，与感染的RosaiDTR对照相比，CD 11 chigh DCs缺陷的约氏疟原虫感染小鼠中促炎细胞因子IFN-γ和TNF-α的全身水平降低。为了进一步阐明CD 11 chigh DCs在感染后期的重要性，我们仅从约氏疟原虫感染的第4天开始用DT处理RosaiDTR/CD 11 c-cre和对照小鼠。引人注目的是，这种方法对CD 4+和CD 8+效应T细胞的活化和IFN-γ产生没有影响。这些结果表明，CD 11 chigh DC在初始阶段在引发效应T细胞应答中起关键作用，但在约氏疟原虫持续感染期间被抑制。
Dendritic cells (DCs) are highly specialized antigen-presenting cells that orchestrate adaptive immune responses to pathogens. During malaria infection pro- and anti-inflammatory T cell responses have to be tightly balanced to ensure parasite clearance without induction of severe immune pathologies. However, the precise role of CD11chigh DCs in this process is still discussed controversially. Here, we demonstrate that long-term depletion of conventional CD11chigh DCs in Plasmodium yoelii (P. yoelii)-infected diphtheria toxin (DT)-treated RosaiDTR/CD11c-cre mice interferes with the activation of CD8+ and CD4+ T cells as well as CD4+Foxp3+ regulatory T cells at early time points during infection. Moreover, systemic levels of the pro-inflammatory cytokines IFN-γ and TNF-α were decreased in P. yoelii-infected mice deficient for CD11chigh DCs compared to infected RosaiDTR controls. To further elucidate the importance of CD11chigh DCs during the later phase of infection, we treated RosaiDTR/CD11c-cre and control mice with DT only from day 4 of P. yoelii infection onward. Strikingly, this approach had no impact on the activation and IFN-γ production of CD4+ and CD8+ effector T cells. These results indicate that CD11chigh DCs play a crucial role in eliciting effector T cell responses during the initial phase, but are dispensable during ongoing infection with P. yoelii.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
16.6
作者：
Hirako, Isabella C.;Ataide, Marco A.;Faustino, Lucas;Assis, Patricia A.;Sorensen, Elizabeth W.;Ueta, Hisashi;Araujo, Natalia M.;Menezes, Gustavo B.;Luster, Andrew D.;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.
影响因子：
6.4
作者：
Abel, Simone;Ueffing, Kristina;Hansen, Wiebke
通讯作者：
Hansen, Wiebke