Pulmonary influenza A virus infection leads to suppression of the innate immune response to dermal injury.
Pulmonary influenza A virus infection leads to suppression of the innate immune response to dermal injury.
复制标题
DOI：
10.1371/journal.ppat.1007212
复制
发表时间：
2018-08
期刊：
影响因子：
6.7
通讯作者：
Jamieson AM
中科院分区：
文献类型：
--
作者：
Crane MJ;Xu Y;Henry WL Jr;Gillis SP;Albina JE;Jamieson AM
先天免疫系统负责身体的许多重要功能，包括对感染的反应、清除癌细胞、愈合伤口和清除外来物质。尽管这些功能在生命中同时发生，但大多数关于先天免疫反应的实验室研究都集中在一种活动上。先天免疫系统如何对身体不同部位同时发生的攻击作出反应尚不清楚。本研究探讨肺部感染对皮肤伤口愈合过程的影响。我们使用了两种互补的损伤模型：切除的尾部伤口和皮下植入聚乙烯醇（PVA）海绵。这些模型允许在急性伤口愈合期间分别评估闭合率和测量细胞和细胞因子反应。当具有这些愈合伤口的小鼠在肺部感染甲型流感病毒（IAV）时，伤口愈合延迟。病毒性肺部感染抑制愈合伤口的先天免疫反应，包括细胞浸润、趋化因子、生长因子和细胞因子。然而，与仅伤口或IAV感染的小鼠相比，感染和愈合伤口的小鼠全身炎症增加，因此没有出现全局免疫抑制。此外，肺部免疫反应在很大程度上未受影响，表明对肺部感染的反应优先于愈合伤口。本研究引入了免疫分诊的概念，即当面临多重损伤时，免疫系统会优先反应。这种模式可能适用于许多涉及先天免疫系统的情况，了解先天免疫系统如何处理多重损伤对于理解它如何有效清除病原体同时对其他炎症事件作出反应至关重要。在自然环境中，先天免疫系统经常面临多重攻击，它必须产生重叠的炎症反应。我们感兴趣的是先天免疫系统如何处理多种同时发生的炎症性损伤，以及对其中一种的反应是否优先。例如，先天免疫系统在介导感染组织中病原体复制的早期控制和伤口愈合的早期阶段都是必不可少的。肺部感染在受伤患者群体中经常发生；因此，我们着手确定呼吸道感染对愈合伤口的影响。为了检验这一点，皮肤伤口愈合的小鼠感染了甲型流感病毒（IAV），这是病毒性肺炎的常见原因。我们发现，肺部感染的先天免疫反应优先于伤口愈合，因为肺中病毒复制的初始控制没有受到影响，而伤口愈合反应受到抑制。很少有人研究免疫反应如何对重叠的炎症性损伤作出反应。我们的研究表明，并非所有的免疫反应都是平等的，先天免疫系统的细胞更倾向于对抗肺部感染，而不是愈合皮肤伤口。这种先天免疫反应的明显优先性开辟了一个新的研究方向。它与许多领域相关，在这些领域中，相互竞争的侮辱可能会改变疾病状态。
The innate immune system is responsible for many important functions in the body including responding to infection, clearing cancerous cells, healing wounds, and removing foreign substances. Although many of these functions happen simultaneously in life, most laboratory studies of the innate immune response focus on one activity. How the innate immune system responds to concurrent insults in different parts of the body is not well understood. This study explores the impact of a lung infection on the cutaneous wound healing process. We used two complimentary models of injury: the excisional tail wound and subcutaneous implantation of polyvinyl alcohol (PVA) sponges. These models allow for assessment of the rate of closure and measurement of cellular and cytokine responses during acute wound healing, respectively. When mice with these healing wounds were infected with influenza A virus (IAV) in the lung there was a delay in wound healing. The viral lung infection suppressed the innate immune response in a healing wound, including cellular infiltrate, chemokines, growth factors, and cytokines. However, there was not a global immune suppression as there was an increase in inflammation systemically in mice with both infection and healing wounds compared to mice with only wounds or IAV infection. In addition, the lung immune response was largely unaffected indicating that responding to a lung infection is prioritized over a healing wound. This study introduces the concept of immune triage, in that when faced with multiple insults the immune system prioritizes responses. This paradigm likely applies to many situations that involve the innate immune system, and understanding how the innate immune system handles multiple insults is essential to understanding how it can efficiently clear pathogens while responding to other inflammatory events. In a natural setting, the innate immune system is frequently faced with multiple insults, against which it must mount overlapping inflammatory responses. We are interested in how the innate immune system deals with multiple, simultaneously occurring inflammatory insults, and if the response to one will take priority. For example, the innate immune system is essential in mediating both the early control of pathogen replication in infected tissue and in the early stages of wound healing. Pulmonary infections occur frequently in injured patient populations; therefore, we set out to determine the impact of a respiratory infection on a healing wound. To examine this, mice with healing dermal wounds were infected with influenza A virus (IAV), a common cause of viral pneumonia. We found that the innate immune response to the lung infection took priority at the expense of the healing wound, in that the initial control of viral replication in the lung was not impacted, while the wound healing response was suppressed. Very little work has been done examining how the immune response can respond to overlapping inflammatory insults. Our work shows that not all immune responses are created equal, and that the cells of the innate immune system are preferentially routed towards fighting a lung infection rather than the healing dermal wound. This apparent prioritization of the innate immune response opens up a new direction of study. It is relevant to many fields where competing insults may alter the disease state.
登录
查看更多内容
影响因子：
8
作者：
Cole SL;Dunning J;Kok WL;Benam KH;Benlahrech A;Repapi E;Martinez FO;Drumright L;Powell TJ;Bennett M;Elderfield R;Thomas C;MOSAIC investigators;Dong T;McCauley J;Liew FY;Taylor S;Zambon M;Barclay W;Cerundolo V;Openshaw PJ;McMichael AJ;Ho LP
通讯作者：
Ho LP
影响因子：
19.6
作者：
Brugués A;Anon E;Conte V;Veldhuis JH;Gupta M;Colombelli J;Muñoz JJ;Brodland GW;Ladoux B;Trepat X
通讯作者：
Trepat X
影响因子：
3.3
作者：
HEDNER, E;VAHLNE, A;HIRSCH, JM
通讯作者：
HIRSCH, JM
影响因子：
6
作者：
He, Lizhi;Marneros, Alexander G.
通讯作者：
Marneros, Alexander G.
影响因子：
38.9
作者：
Daubin, C;Vincent, S;Charbonneau, P
通讯作者：
Charbonneau, P