Distinct Tissue Damage and Microbial Cues Drive Neutrophil and Macrophage Recruitment to Thermal Injury.
Distinct Tissue Damage and Microbial Cues Drive Neutrophil and Macrophage Recruitment to Thermal Injury.
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DOI：
10.1016/j.isci.2020.101699
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发表时间：
2020-11-20
期刊：
影响因子：
5.8
通讯作者：
Huttenlocher A
中科院分区：
文献类型：
--
作者：
Barros-Becker F;Squirrell JM;Burke R;Chini J;Rindy J;Karim A;Eliceiri KW;Gibson A;Huttenlocher A
组织损伤会触发快速的先天免疫反应，介导宿主防御。之前我们报道过，斑马鱼幼虫鳍的热损伤会破坏胶原蛋白组织，并诱导强大且可能具有破坏性的先天免疫反应。驱动间质组织中破坏性与保护性中性粒细胞炎症的机制仍不清楚。在这里，我们确定了组织微环境中的不同线索，这些线索差异性地驱动中性粒细胞和巨噬细胞对无菌损伤的反应。通过实时成像，我们在无胶原区域中发现了中性粒细胞的运动区，但巨噬细胞没有，并确定了白细胞介素 6 (IL-6) 受体信号传导在中性粒细胞对热损伤反应中的特定作用。 IL-6 受体突变体显示中性粒细胞募集受损，导致无菌热损伤，而这在铜绿假单胞菌感染的组织中并不存在。这些发现确定了中性粒细胞募集到无菌和微生物损伤线索期间的不同信号网络，并提供了限制潜在破坏性中性粒细胞炎症的框架。中性粒细胞（而非巨噬细胞）快速迁移到烧伤无胶原区 ATP 或 ROS 的缺乏会明显影响中性粒细胞和巨噬细胞的募集 缺乏 Il-6r 会强烈影响中性粒细胞募集到无菌烧伤创面 在铜绿假单胞菌感染期间可以挽救中性粒细胞募集缺陷 Il-6r 中性粒细胞募集缺陷
Tissue damage triggers a rapid innate immune response that mediates host defense. Previously we reported that thermal damage of the larval zebrafish fin disrupts collagen organization and induces a robust and potentially damaging innate immune response. The mechanisms that drive damaging versus protective neutrophil inflammation in interstitial tissues remain unclear. Here we identify distinct cues in the tissue microenvironment that differentially drive neutrophil and macrophage responses to sterile injury. Using live imaging, we found a motile zone for neutrophils, but not macrophages, in collagen-free regions and identified a specific role for interleukin-6 (IL-6) receptor signaling in neutrophil responses to thermal damage. IL-6 receptor mutants show impaired neutrophil recruitment to sterile thermal injury that was not present in tissues infected with Pseudomonas aeruginosa. These findings identify distinct signaling networks during neutrophil recruitment to sterile and microbial damage cues and provide a framework to limit potentially damaging neutrophil inflammation. Neutrophils, but not macrophages, rapidly migrate into a burn collagen-free zone Lack of ATP or ROS affects neutrophil and macrophage recruitment distinctively Absence of Il-6r strongly affects neutrophil recruitment to a sterile burn wound Il-6r neutrophil recruitment defect can be rescued during P. aeruginosa infection Microbiology and Immunology
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影响因子：
14.9
作者：
Dobson L;Reményi I;Tusnády GE
通讯作者：
Tusnády GE
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
DOI：
10.1097/bcr.0b013e31829b36d6
发表时间：
2014-01
期刊：
Journal of burn care & research : official publication of the American Burn Association
影响因子：
--
作者：
Bayliss J;Delarosa S;Wu J;Peterson JR;Eboda ON;Su GL;Hemmila M;Krebsbach PH;Cederna PS;Wang SC;Xi C;Levi B
通讯作者：
Levi B
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.4
作者：
de Oliveira, Sofia;Lopez-Munoz, Azucena;Mulero, Victoriano
通讯作者：
Mulero, Victoriano