Marked alterations of neutrophil functions during sepsis-induced immunosuppression
Marked alterations of neutrophil functions during sepsis-induced immunosuppression
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DOI：
10.1189/jlb.4a0415-168rr
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发表时间：
2015-12-01
影响因子：
5.5
通讯作者：
Monneret, Guillaume
中科院分区：
文献类型：
--
作者：
Demaret, Julie;Venet, Fabienne;Monneret, Guillaume
严重脓毒症严重损害先天免疫和适应性免疫，并导致脓毒症诱导的免疫抑制。虽然中性粒细胞代表了抵抗感染的第一道防线，但对脓毒症后几天的表型和功能知之甚少，此时免疫抑制期最大（即，在D 3和8之间）。本研究的目的是首次使用表型和功能研究对免疫抑制脓毒症患者（第3-4天和第6-8天）的中性粒细胞变化进行全面评价。此外，还评估了这些参数与有害结局的潜在相关性。收集43例感染性休克患者的外周血，并与23名健康对照者进行比较。在脓毒症患者中，我们的结果突出了显著改变的中性粒细胞趋化性（功能和趋化因子受体表达）、氧化爆发和乳铁蛋白含量以及循环未成熟粒细胞（即，CD10（dim）CD16（dim））。这些方面与感染性休克后死亡风险增加相关。相反，吞噬和激活能力是保守的。总之，败血症发作后几天，循环中性粒细胞表现出表型、功能和形态学改变。这些功能障碍可能参与败血症诱导的免疫抑制的有害作用。目前的研究结果为脓毒性休克后医院感染的机制提供了新的视角。它们值得在更大规模的临床研究和重现这些变化的动物模型中进一步研究。
Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10(dim)CD16(dim)). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations.