Dendritic cell modification of neutrophil responses to infection after burn injury.
Dendritic cell modification of neutrophil responses to infection after burn injury.
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DOI：
10.4049/jimmunol.0903619
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Toliver-Kinsky T
中科院分区：
文献类型：
--
作者：
Bohannon J;Cui W;Sherwood E;Toliver-Kinsky T
烧伤患者由于伤口暴露增加和许多免疫功能受损而极易感染。树突状细胞（DC）在激活许多免疫应答中是重要的，这些免疫应答对于清除感染是必不可少的。我们已经发现，预防性治疗烧伤小鼠与DC生长因子fms样酪氨酸激酶-3配体（FL）显着增加抵抗烧伤伤口感染的DC依赖性的方式，这是密切相关的细菌清除增强。然而，由于DC通常不是杀微生物的，DC调节增强细菌清除的机制尚不清楚。由于中性粒细胞对皮肤伤口的快速反应，以及报道的DC和中性粒细胞之间的相互作用，我们研究了中性粒细胞在FL介导的对烧伤伤口感染的抵抗中的作用。通过中性粒细胞耗竭、中性粒细胞补充和FL治疗后中性粒细胞趋化性评估，在体内和体外检查了这一点。为了测试DC的参与，在FL处理期间利用CD 11 c-DTR转基因小鼠来消耗DC。研究表明，中性粒细胞确实在FL介导的对烧伤创面感染的抵抗中发挥关键作用。此外，FL治疗烧伤后增强了嗜中性粒细胞介导的控制细菌传播，中性粒细胞迁移能力，MPO生产，在DC依赖性的方式。这项研究的结果提供了新的见解免疫机制，可以提供保护，防止感染后烧伤。
Burn patients are highly susceptible to infections due to increased exposure through wounds and impairments in a number of immune functions. Dendritic cells (DCs) are important in activation of numerous immune responses that are essential for the clearance of infections. We have found that prophylactic treatment of burn-injured mice with the DC growth factor fms-like tyrosine kinase-3 ligand (FL) significantly increases resistance to burn wound infections in a DC-dependent manner that is correlated closely with enhanced bacterial clearance. However, as DCs are not typically microbicidal, the mechanisms by which DC modulation enhances bacterial clearance are not known. Due to the rapid response of neutrophils to cutaneous wounds, and the reported interactions between DCs and neutrophils, we investigated the role of neutrophils in FL-mediated resistance to burn wound infection. This was examined both in vivo and in vitro through neutrophil depletion, supplementation of neutrophils, and assessment of neutrophil chemotaxis following FL treatment. To test the involvement of DCs, CD11c-DTR transgenic mice were utilized to deplete DCs during FL treatment. Studies revealed that neutrophils do play a critical role in FL-mediated resistance to a burn wound infection. Additionally, treatment with FL after a burn injury enhances neutrophil-mediated control of bacterial spread, neutrophil migratory capacity, and MPO production, in a DC-dependent manner. The results of this study provide new insight into immunological mechanisms that can offer protection against infection after burn injury.
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