CD11b⁺, Ly6G⁺ cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection.
CD11b⁺, Ly6G⁺ cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection.
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DOI：
10.1371/journal.ppat.1002374
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发表时间：
2011-11
期刊：
影响因子：
6.7
通讯作者：
Norbury CC
中科院分区：
文献类型：
--
作者：
Fischer MA;Davies ML;Reider IE;Heipertz EL;Epler MR;Sei JJ;Ingersoll MA;Rooijen NV;Randolph GJ;Norbury CC
先天免疫系统的目标是在有效的适应性免疫应答开始之前在感染部位遏制病原体。然而，效应器机制必须保持在检查中以对抗病原体，同时限制由这些作用引起的组织的不期望的破坏。在这里，我们证明了先天免疫效应细胞含有外周痘病毒感染，防止病毒的全身传播。这些先天性免疫效应细胞主要由CD 11b + Ly 6C + Ly 6 G-单核细胞组成，最初在感染部位积累，然后补充并最终被CD 11b + Ly 6C + Ly 6 G+细胞取代。CD 11b + Ly 6C + Ly 6 G+细胞的表型类似于中性粒细胞，但中性粒细胞的浸润通常发生在单核细胞积聚之前，而不是之后。事实上，似乎浸润耳中VACV感染部位的CD 11b + Ly 6C + Ly 6 G+细胞在表型上不同于中性粒细胞和单核细胞/巨噬细胞的经典描述。我们发现，CD 11b + Ly 6C + Ly 6 G+细胞产生I型干扰素和大量的活性氧。我们还观察到Ly 6 G+细胞的耗竭导致感染部位的组织损伤急剧增加。在不存在活性氧物质的情况下，组织损伤也会增加，尽管活性氧物质通常被认为是对组织的损伤而不是保护。这些数据表明，存在一个专门的群体的CD 11b + Ly 6C + Ly 6 G+细胞，浸润病毒感染的网站晚，并保护感染的组织从免疫介导的损伤，通过生产活性氧。调节该细胞群体的作用可以提供干预以防止先天免疫介导的组织破坏。在自然病毒感染期间，小剂量的感染性病毒沉积在外周感染部位，然后是“竞赛”包围，其中复制病毒试图“超越”宿主的响应免疫系统。在感染的早期阶段，先天免疫系统必须在发展有效的适应性反应之前控制感染。在这里，我们的特点是先天免疫系统的细胞移动到外周病毒感染的网站，我们发现，这些细胞的一个子集显示非典型表达的细胞表面分子，浸润的时间，和功能。这些细胞通过产生活性氧分子来保护受感染的组织免受损害，活性氧分子被广泛认为会增加组织损伤。因此，我们的研究结果表明，在外周病毒感染期间，控制先天免疫系统功能的典型规则被改变，以防止组织损伤。
The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b+Ly6C+Ly6G- monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b+Ly6C+Ly6G+ cells. The phenotype of the CD11b+Ly6C+Ly6G+ cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b+Ly6C+Ly6G+ cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b+Ly6C+Ly6G+ cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G+ cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b+Ly6C+Ly6G+ cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction. During a natural virus infection, small doses of infectious virus are deposited at a peripheral infection site, and then a “race” ensues, in which the replicating virus attempts to “outpace” the responding immune system of the host. In the early phases of infection, the innate immune system must contain the infection prior to the development of an effective adaptive response. Here we have characterized the cells of the innate immune system that move to a site of peripheral virus infection, and we find that a subset of these cells display atypical expression of cell surface molecules, timing of infiltration, and function. These cells protect the infected tissue from damage by producing reactive oxygen molecules, which are widely accepted to increase tissue damage. Therefore our findings indicate that during a peripheral virus infection, the typical rules governing the function of the innate immune system are altered to prevent tissue damage.
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LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
5.7
作者：
Jaffe, ML;Arai, H;Nabel, GJ
通讯作者：
Nabel, GJ
影响因子：
15.3
作者：
Karupiah, Gunasegaran;Harris, Nicholas
通讯作者：
Harris, Nicholas
影响因子：
6.7
作者：
Komatsu, J.;Koyama, H.;Aratani, Y.
通讯作者：
Aratani, Y.
影响因子：
4.4
作者：
Kusmartsev, SA;Li, Y;Chen, SB
通讯作者：
Chen, SB