Antibody therapy against the type-III toxin secretion system on lung infection and sepsis associated with Pseudomonas aeruuginosa

铜绿假单胞菌肺部感染通常与高死亡率相关，特别是在接受重症监护的患者中。根据III型分泌表型，铜绿假单胞菌肺部感染可引起急性器官损伤和脓毒生理。本研究在铜绿假单胞菌脓毒症的两种动物模型中，研究了兔源性多克隆抗体PcrV（一种参与铜绿假单胞菌III型分泌毒素易位的蛋白）的作用。在一项小鼠生存研究中，在空气中注入致死剂量的铜绿假单胞菌后静脉注射抗pcrv IgG可使小鼠完全存活。在铜绿假单胞菌诱导的脓毒性休克兔肺损伤模型中，与用非特异性对照IgG进行类似处理的动物相比，经肺内或静脉注射抗pcrv IgG治疗的动物肺损伤、菌血症、血浆TNF-α显著减少，与休克相关的血流动力学参数显著改善。抗pcrv抗体F（ab’）_2具有与全抗pcrv IgG相当的保护作用。这些结果证明，抗pcrv IgG的治疗性管理阻断了铜绿假单胞菌III型分泌系统介导的毒力，防止感染性休克和死亡，并且这些保护作用在很大程度上是不依赖于fc的。我们得出结论，抗体治疗中和III型分泌系统对致命铜绿假单胞菌感染具有显著的潜力

Pseudomonas aeruginosa lung infections are frequently associated with high mortality rates, particularly in patients receiving intensive care. Depending on the type III secretion phenotype, P. aeruginosa causes acute organ damage and septic physiology in P. aeruginosa lung infections. In this study, the effects of rabbit-derived polyclonal antibody against PcrV, a protein involved in the translocation of type III secreted toxins of Pseudomonas aeruginosa, was investigated in two animal models of P. aeruginosa sepsis. In a mouse survival study, the intravenous administration of anti-PcrV IgG after the airspace instillation of a lethal dose of P. aeruginosa resulted in the complete survival of the animals. In a rabbit model of septic shock associated with P. aeruginosa-induced lung injury, animals treated with anti-PcrV IgG intracheally or intravenously had significant decreases in lung injury, bacteremia, plasma TNF-α, and significant improvement in the hemodynamic parameters associated with shock compared to animals treated in a similar manner with non-specific control IgG. The administration of anti-PcrV F(ab')_2 showed protective effects comparable to whole anti-PcrV IgG. These results document that the therapeutic administration of anti-PcrV IgG blocks the type III secretion system-mediated virulence of P. aeruginosa and prevents septic shock and death, and that these protective effects are largely Fc-independent. We conclude that antibody therapy neutralizing the type III secretion system has significant potential against lethal P. aeruginosa infections