Clatworthy Menna R, Smith Kenneth G C
The Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, CB2 2XY, UK.
J Exp Med. 2004 Mar 1;199(5):717-23. doi: 10.1084/jem.20032197. Epub 2004 Feb 23.
The immune response to infection must be controlled to ensure it is optimal for defense while avoiding the consequences of excessive inflammation, which include fatal septic shock. Mice deficient in FcgammaRIIb, an inhibitory immunoglobulin G Fc receptor, have enhanced immune responses. Therefore, we examined whether FcgammaRIIb controls the response to Streptococcus pneumoniae. Macrophages from FcgammaRIIb-deficient mice showed increased antibody-dependent phagocytosis of pneumococci in vitro, and consistent with this infected FcgammaRIIb-deficient mice demonstrated increased bacterial clearance and survival. In contrast, previously immunized FcgammaRIIb-deficient mice challenged with large inocula showed reduced survival. This correlated with increased production of the sepsis-associated cytokines tumor necrosis factor alpha and interleukin 6. We propose that FcgammaRIIb controls the balance between efficient pathogen clearance and the cytokine-mediated consequences of sepsis, with potential therapeutic implications.
必须控制对感染的免疫反应，以确保其在防御方面达到最佳状态，同时避免过度炎症带来的后果，其中包括致命的脓毒性休克。缺乏抑制性免疫球蛋白G Fc受体FcγRIIb的小鼠具有增强的免疫反应。因此，我们研究了FcγRIIb是否控制对肺炎链球菌的反应。来自FcγRIIb缺陷小鼠的巨噬细胞在体外显示出对肺炎球菌的抗体依赖性吞噬作用增强，与此一致，感染的FcγRIIb缺陷小鼠表现出细菌清除率增加和存活率提高。相比之下，先前免疫过的FcγRIIb缺陷小鼠在接受大量接种物攻击后存活率降低。这与脓毒症相关细胞因子肿瘤坏死因子α和白细胞介素6的产生增加有关。我们提出，FcγRIIb控制有效病原体清除与脓毒症细胞因子介导后果之间的平衡，具有潜在的治疗意义。
