Innate immune system favors emergency monopoiesis at the expense of DC‐differentiation to control systemic bacterial infection in mice
Innate immune system favors emergency monopoiesis at the expense of DC‐differentiation to control systemic bacterial infection in mice
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先天免疫系统有利于紧急垄断，但以牺牲 DC-分化为代价来控制小鼠的全身细菌感染
DOI：
10.1002/eji.201545530
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发表时间：
2015
影响因子：
5.4
通讯作者：
Autenrieth SE
中科院分区：
文献类型：
--
作者：
Pasquevich KA;Bieber K;Günter M;Grauer M;Pötz O;Schleicher U;Biedermann T;Beer-Hammer S;Bühring HJ;Rammensee HG;Zender L;Autenrieth IB;Lengerke C;Autenrieth SE
DC是专业的APC，在启动T细胞反应以对抗感染方面发挥关键作用。然而，各种病原体的全身性细菌感染会导致人和小鼠的DC耗竭。病原体诱导的DC耗竭的机制尚不清楚。先前，我们发现感染小肠结肠炎耶尔森氏菌(Ye)的小鼠已经损害了DC的新生发育，这是DC耗尽的原因之一。在这里，我们扩展这些研究，以深入了解DC耗竭的分子机制，以及不同细菌对DC发育的影响。我们发现，在全身感染不同的革兰氏阳性和革兰氏阴性细菌后，致力于DC血统的骨髓(BM)造血祖细胞的数量减少。这与Ye感染后骨髓中承诺的单核细胞祖细胞和脾中成熟单核细胞的TLR4和干扰素-γ−信号依赖性增加有关。过继转移实验表明，感染诱导的单核细胞生成是以DC发育为代价的。我们的数据为造血祖细胞对全身细菌感染的一般反应提供了证据，以增加单核细胞的产生，从而增加用于病原体控制的天然免疫细胞的可用性，而DC发育受损导致DC耗尽，可能导致细菌败血症的一过性免疫抑制。
DCs are professional APCs playing a crucial role in the initiation of T‐cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC‐depletion in humans and mice. The mechanisms of pathogen‐induced DC‐depletion remain poorly understood. Previously, we showed that mice infected withYersinia enterocolitica(Ye) had impaired de novo DC‐development, one reason for DC‐depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC‐depletion and the impact of different bacteria on DC‐development. We show that the number of bone marrow (BM) hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram‐positive and Gram‐negative bacteria. This is associated with a TLR4‐ and IFN‐γ−signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye‐infection. Adoptive transfer experiments revealed that infection‐induced monopoiesis occurs at the expense of DC‐development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC‐development leads to DC‐depletion, possibly driving transient immunosuppression in bacterial sepsis.
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影响因子：
6.7
作者：
Belyaev NN;Biró J;Langhorne J;Potocnik AJ
通讯作者：
Potocnik AJ
影响因子：
30.5
作者：
Naik, Shalin H.;Sathe, Priyanka;Shortman, Ken
通讯作者：
Shortman, Ken
影响因子：
56.9
作者：
HUANG, S;HENDRIKS, W;AGUET, M
通讯作者：
AGUET, M
抗原特异性 T 淋巴细胞在体内调节脂多糖诱导的树突状细胞凋亡。
影响因子：
4.4
作者：
T. D. Smedt;B. Pajak;G. Klaus;R. Noelle;J. Urbain;O. Leo;M. Moser
通讯作者：
M. Moser
影响因子：
30.5
作者：
Onai, Nobuyuki;Obata-Onai, Aya;Manz, Markus G.
通讯作者：
Manz, Markus G.