Contribution of Dendritic Cell Responses to Sepsis-Induced Immunosuppression and to Susceptibility to Secondary Pneumonia.
Contribution of Dendritic Cell Responses to Sepsis-Induced Immunosuppression and to Susceptibility to Secondary Pneumonia.
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DOI：
10.3389/fimmu.2018.02590
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发表时间：
2018
影响因子：
7.3
通讯作者：
Roquilly A
中科院分区：
文献类型：
--
作者：
Bouras M;Asehnoune K;Roquilly A
树突状细胞（DC）是骨髓来源的细胞，在外周组织中持续繁殖。在感染过程中，树突状细胞在先天免疫和适应性免疫之间发挥着重要的作用。肺炎是由病原体引发的肺部炎症，其特征是过度释放炎症细胞因子，激活先天性和获得性免疫。肺炎会导致快速而持久的继发感染易感状态，即所谓的脓毒症引起的免疫抑制状态。在这篇综述中，我们重点关注 DC 在这种免疫抑制状态发展中的作用。在炎症早期，活化的 DC 的特征是抗原（交叉）呈递新遇到的抗原的能力下降以及免疫原性细胞因子的产生减少，脓毒症诱导的免疫抑制主要是由于已成熟的未成熟 DC 的消耗所致。在后期，新形成的呼吸道未成熟树突状细胞通过炎症留下的免疫恐慌进行局部编程，以诱导耐受。致耐受性Blimp1+ DC 产生抑制性细胞因子，例如肿瘤生长因子-B，并参与维持以Treg 细胞积累为显着特征的局部致耐受环境。在小鼠中，树突状细胞免疫原性功能的恢复可以恢复对病原体的粘膜免疫反应。在人类中，脓毒症或创伤期间糖皮质激素对炎症的调节保留了 DC 的免疫原性功能，并与对继发性肺炎的抵抗力相关。最后，我们提出，炎症期间和之后 DC 的变化可以用作继发性肺炎易感性的生物标志物，并且是有希望的治疗靶点，以提高继发性肺炎患者的预后。
Dendritic cells (DCs) are bone marrow derived cells which continuously seed in peripheral tissue. During infection, DCs play an essential interface between innate and adaptive immunity. Pneumonia is a lung inflammation triggered by pathogens and is characterized by excessive release of inflammatory cytokines that activate innate and acquired immunity. Pneumonia induces a rapid and protracted state of susceptibility to secondary infection, a state so-called sepsis-induced immunosuppression. In this review, we focus on the role of DCs in the development of this state of immunosuppression. Early during inflammation, activated DCs are characterized by decreased capacity of antigen (cross)- presentation of newly encountered antigens and decreased production of immunogenic cytokines, and sepsis-induced immunosuppression is mainly explained by a depletion of immature DCs which had all become mature. At a later stage, newly formed respiratory immature DCs are locally programmed by an immunological scare left-over by inflammation to induce tolerance. Tolerogenic Blimp1+ DCs produce suppressive cytokines such as tumor growth factor-B and participate to the maintenance of a local tolerogenic environment notably characterized by accumulation of Treg cells. In mice, the restoration of the immunogenic functions of DCs restores the mucosal immune response to pathogens. In humans, the modulation of inflammation by glucocorticoid during sepsis or trauma preserves DC immunogenic functions and is associated with resistance to secondary pneumonia. Finally, we propose that the alterations of DCs during and after inflammation can be used as biomarkers of susceptibility to secondary pneumonia and are promising therapeutic targets to enhance outcomes of patients with secondary pneumonia.
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影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
影响因子：
20.3
作者：
Cao, Yun;Bender, Ingrid K.;Lu, Nick Z.
通讯作者：
Lu, Nick Z.
影响因子：
4.4
作者：
Efron, PA;Martins, A;Moldawer, LL
通讯作者：
Moldawer, LL
影响因子：
32.4
作者：
Baratin, Myriam;Foray, Chloe;Lawrence, Toby
通讯作者：
Lawrence, Toby
影响因子：
6.7
作者：
Beshara R;Sencio V;Soulard D;Barthélémy A;Fontaine J;Pinteau T;Deruyter L;Ismail MB;Paget C;Sirard JC;Trottein F;Faveeuw C
通讯作者：
Faveeuw C