Contribution of natural killer cells to the pathogenesis of septic shock induced by Streptococcus pyogenes in mice
Contribution of natural killer cells to the pathogenesis of septic shock induced by Streptococcus pyogenes in mice
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DOI：
10.1086/428501
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发表时间：
2005-04-15
影响因子：
6.4
通讯作者：
Medina, E
中科院分区：
文献类型：
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作者：
Goldmann, O;Chhatwal, GS;Medina, E
自然杀伤(NK)细胞是天然免疫系统的重要组成部分，与感染性休克的发病机制密切相关。在本研究中，在A组链球菌感染的小鼠模型中，研究了NK细胞在化脓性链球菌致败血症休克中的相对作用，该模型与人类类似。用抗去唾液神经节-N-四糖神经酰胺抗体体内注射去唾液酸神经节-N-四糖神经酰胺抗体去除C3H/HEN小鼠的NK细胞，然后检测其对化脓性链球菌感染的反应。在A组链球菌感染期间，NK细胞耗尽的小鼠比未耗尽的对照组小鼠存活时间延长，疾病发展缓慢。NK细胞耗竭小鼠对化脓性链球菌的耐药性增强与感染早期血清促炎细胞因子水平有关，如干扰素-γ、白介素12和白介素6水平远低于非耗竭对照组小鼠。NK细胞缺陷突变小鼠对化脓性链球菌的抵抗力也高于相应的对照小鼠。我们的结论是，NK细胞通过放大炎症反应，在化脓性链球菌诱导的感染性休克的进展中起重要作用。
Natural killer (NK) cells are critical components of the innate immune system and have been implicated in the pathogenesis of septic shock. In the present study, the relative contribution of NK cells to the development of Streptococcus pyogenes-induced septic shock was investigated in a mouse model of group A streptococcal infection that resembles the development of this condition in humans. C3H/HeN mice were depleted of NK cells by in vivo administration of anti-asialo ganglio-N-tetraosylceramide antibodies and then were examined for their response to infection with S. pyogenes. NK cell-depleted mice exhibited increased survival times and slower development of disease during group A streptococcal infection than did nondepleted control mice. The augmented resistance to S. pyogenes observed in NK cell-depleted mice was associated with serum levels of proinflammatory cytokines such as interferon-gamma, interleukin (IL)-12, and IL-6 during the early phase of infection that were much lower than those detected in nondepleted control mice. NK cell-deficient mutant mice were also more resistant to S. pyogenes than were the corresponding control mice. We conclude that NK cells, by amplifying the inflammatory response, significantly contribute to the progression of S. pyogenes-induced septic shock.