G-CSF drives a posttraumatic immune program that protects the host from infection.
G-CSF drives a posttraumatic immune program that protects the host from infection.
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DOI：
10.4049/jimmunol.1302752
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发表时间：
2014-03-01
期刊：
影响因子：
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通讯作者：
McCormack FX
中科院分区：
文献类型：
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作者：
Gardner JC;Noel JG;Nikolaidis NM;Karns R;Aronow BJ;Ogle CK;McCormack FX
外伤通常被认为对免疫系统有抑制作用，导致感染的易感性增加。矛盾的是，我们发现皮肤的热损伤诱导了小鼠免受致命的肺炎克雷伯氏菌肺部攻击的强大的时间依赖性保护。这种保护性反应是中性粒细胞依赖性的，并且暂时与中性粒细胞的系统性增加相关，这是由于造血向骨髓谱系的重新优先化而导致的。骨髓中 STAT3 的显着且特异性激活先于该区室中的骨髓转移，这与 STAT3 激活血清细胞因子 G-CSF 和 IL-6 的持续增加相关。烧伤后血清 G-CSF 升高的中和在很大程度上阻断了骨髓细胞中 STAT3 的激活，逆转了造血变化和全身性中性粒细胞增多。每日施用重组 G-CSF 足以重现损伤引起的变化，包括造血重新优先化和免受肺炎克雷伯菌肺部攻击的保护。对人类创伤后基因表达模式的分析表明，它们也与 G-CSF 作为激活先天免疫反应和抑制适应性免疫反应的开关的作用一致。我们的研究结果表明，G-CSF STAT3 轴构成了损伤诱导的关键保护机制，可降低创伤后感染的风险。
Traumatic injury is generally considered to have a suppressive effect on the immune system, resulting in increased susceptibility to infection. Paradoxically, we found that thermal injury to the skin induced a robust time-dependent protection of mice from a lethal Klebsiella pneumoniae pulmonary challenge. The protective response was neutrophil dependent and temporally associated with a systemic increase in neutrophils resulting from a reprioritization of hematopoiesis toward myeloid lineages. A prominent and specific activation of STAT3 in the bone marrow preceded the myeloid shift in that compartment, in association with durable increases in STAT3 activating serum cytokines G-CSF and IL-6. Neutralization of the post burn rise in serum G-CSF largely blocked STAT3 activation in marrow cells, reversing the hematopoietic changes and systemic neutrophilia. Daily administration of recombinant G-CSF was sufficient to recapitulate the changes induced by injury including hematopoietic reprioritization and protection from pulmonary challenge with K. pneumoniae. Analysis of posttraumatic gene expression patterns in humans reveals that they are also consistent with a role for G-CSF as a switch that activates innate immune responses and suppresses adaptive immune responses. Our findings suggest that the G-CSF STAT3 axis constitutes a key protective mechanism induced by injury to reduce the risk of post-traumatic infection.