The absence of DNGR-1 is dangerous Conventional type 1 dendritic cells (cDC1s) can sense tissue damage via DNGR-1, which binds F-actin exposed by necrotic cells. DNGR-1 activation favors cross-presentation, the process by which extracellular antigens are processed and presented to CD8+ T cells via major histocompatibility complex class I molecules. Del Fresno et al. studied mice lacking DNGR-1 and found that DNGR-1 also has anti-inflammatory effects (see the Perspective by Salazar and Brown). It inhibits the secretion of the chemokine CXCL2 by cDC1s, which, in turn, limits neutrophil recruitment. Thus, DNGR-1 connects cell-death sensing with a mechanism of damage control. Science, this issue p. 351; see also p. 292 A damage-sensing receptor hits the brakes to control the extent of tissue damage during infection, injury, and inflammation. Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell–independent and attributable to increased neutrophilia in DNGR-1–deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1–mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.

中文翻译：

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树突状细胞中的 DNGR-1 通过抑制中性粒细胞募集来限制组织损伤

DNGR-1 的缺失是危险的 传统 1 型树突细胞 (cDC1s) 可以通过 DNGR-1 感知组织损伤，DNGR-1 结合坏死细胞暴露的 F-肌动蛋白。DNGR-1 激活有利于交叉呈递，即处理细胞外抗原并通过主要组织相容性复合体 I 类分子呈递给 CD8+ T 细胞的过程。德尔弗雷斯诺等。研究了缺乏 DNGR-1 的小鼠，发现 DNGR-1 还具有抗炎作用（参见 Salazar 和 Brown 的观点）。它通过 cDC1s 抑制趋化因子 CXCL2 的分泌，从而限制中性粒细胞的募集。因此，DNGR-1 将细胞死亡传感与损伤控制机制联系起来。科学，这个问题 p。351; 另见第。292 在感染、损伤和炎症过程中，损伤感应受体会踩刹车来控制组织损伤的程度。宿主损伤会触发限制组织损伤的反馈机制。传统的 1 型树突细胞 (cDC1s) 表达树突细胞自然杀伤凝集素组受体-1 (DNGR-1)，由基因 Clec9a 编码，可感知组织损伤并有利于死细胞物质向 CD8+ T 细胞的交叉呈递。在这里，我们发现 DNGR-1 还减少了小鼠无菌和感染性组织损伤引起的宿主破坏性炎症反应。在全身性白色念珠菌感染期间，DNGR-1 缺乏会导致雨桐素诱导的坏死性胰腺炎恶化和病理增加，而不会影响真菌负担。这种效应不依赖于 B 和 T 细胞，可归因于 DNGR-1 缺陷环境中中性粒细胞增多。从机制上讲，DNGR-1 参与激活 SHP-1 并抑制念珠菌感染期间 cDC1s 产生的 MIP-2（由 Cxcl2 编码）。因此，这抑制了中性粒细胞的募集并促进了疾病耐受性。因此，DNGR-1 介导的 cDC1s 对损伤的感知可作为控制组织损伤、先天免疫和免疫病理学的变阻器。