Mast cell IL-6 improves survival from Klebsiella pneumonia and sepsis by enhancing neutrophil killing.
Mast cell IL-6 improves survival from Klebsiella pneumonia and sepsis by enhancing neutrophil killing.
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DOI：
10.4049/jimmunol.181.8.5598
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发表时间：
2008-10-15
期刊：
影响因子：
--
通讯作者：
Wolters PJ
中科院分区：
文献类型：
--
作者：
Sutherland RE;Olsen JS;McKinstry A;Villalta SA;Wolters PJ
多效性细胞因子白介素6(IL-6)对细菌感染的生存有有利和有害的影响。虽然许多先天免疫细胞产生IL-6，但人们对体内相关来源及其对宿主对严重细菌感染反应的贡献的性质知之甚少。为了检验这些作用，我们对肥大细胞特异性IL-6缺陷小鼠进行了盲肠结扎和穿孔的感染性腹膜炎模型，发现这些小鼠的存活率明显低于对照组。在鼻腔或腹膜内接种肺炎克雷伯菌后，IL-6-/-小鼠比野生型对照组存活的可能性更小，死亡时肺部和腹膜中的细菌数量更多，但没有炎细胞。同样，肥大细胞特异性IL-6缺陷的小鼠在腹膜内感染后存活率降低，肺炎克雷伯菌数量增加。缺乏IL-6的中性粒细胞有更多的活细胞内肺炎克雷伯菌，这表明细胞内杀伤受损导致IL-6-/-小鼠的清除减少。这些结果表明，肥大细胞IL-6是肺炎克雷伯菌感染和脓毒症后存活的关键介质，并表明IL-6通过增强中性粒细胞对细菌的杀灭而保护死亡。
The pleiotropic cytokine interleukin 6 (IL-6) has favorable and harmful effects on survival from bacterial infections. While many innate immune cells produce IL-6, little is known about relevant sources in vivo and the nature of its contributions to host responses to severe bacterial infections. To examine these roles, we subjected mast cell-specific IL-6-deficient mice to the cecal ligation and puncture model of septic peritonitis, finding that survival in these mice is markedly worse than in controls. Following intranasal or intraperitoneal inoculation with Klebsiella pneumoniae, IL-6-/- mice are less likely to survive than wild-type controls and at the time of death have higher numbers of bacteria but not inflammatory cells in lungs and peritoneum. Similarly, mast cell-specific IL-6-deficient mice have diminished survival and higher numbers of K. pneumoniae following intraperitoneal infection. Neutrophils lacking IL-6 have greater numbers of live intracellular K. pneumonia, suggesting impaired intracellular killing contributes to reduced clearance in IL-6-/- mice. These results establish that mast cell IL-6 is a critical mediator of survival following K. pneumoniae infection and sepsis and suggest that IL-6 protects from death by augmenting neutrophil killing of bacteria.
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DOI：
10.1165/ajrcmb.10.5.8179909
发表时间：
1994-05-01
影响因子：
6.4
作者：
BRADDING, P;ROBERTS, JA;HOLGATE, ST
通讯作者：
HOLGATE, ST
影响因子：
3.1
作者：
BrougHolub, E;Toews, GB;Standiford, TJ
通讯作者：
Standiford, TJ
影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
3.1
作者：
DALRYMPLE, SA;LUCIAN, LA;MURRAY, R
通讯作者：
MURRAY, R
影响因子：
3.1
作者：
Laichalk, LL;Kunkel, SL;Standiford, TJ
通讯作者：
Standiford, TJ