Department of Immunology and Inflammation, Istituto Clinico Humanitas, Scientific Institute for Hospitalization and Cure, 20089Rozzano, Italy.
J Immunol. 2011 May 1;186(9):5425-34. doi: 10.4049/jimmunol.1002035. Epub 2011 Mar 25.
Chronic lung infections by Pseudomonas aeruginosa strains are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Although there is no clear evidence for a primary defect in the immune system of CF patients, the host is generally unable to clear P. aeruginosa from the airways. PTX3 is a soluble pattern recognition receptor that plays nonredundant roles in the innate immune response to fungi, bacteria, and viruses. In particular, PTX3 deficiency is associated with increased susceptibility to P. aeruginosa lung infection. To address the potential therapeutic effect of PTX3 in P. aeruginosa lung infection, we established persistent and progressive infections in mice with the RP73 clinical strain RP73 isolated from a CF patient and treated them with recombinant human PTX3. The results indicated that PTX3 has a potential therapeutic effect in P. aeruginosa chronic lung infection by reducing lung colonization, proinflammatory cytokine levels (CXCL1, CXCL2, CCL2, and IL-1β), and leukocyte recruitment in the airways. In models of acute infections and in in vitro assays, the prophagocytic effect of PTX3 was maintained in C1q-deficient mice and was lost in C3- and Fc common γ-chain-deficient mice, suggesting that facilitated recognition and phagocytosis of pathogens through the interplay between complement and FcγRs are involved in the therapeutic effect mediated by PTX3. These data suggested that PTX3 is a potential therapeutic tool in chronic P. aeruginosa lung infections, such as those seen in CF patients.
铜绿假单胞菌慢性肺部感染是囊性纤维化（CF）患者发病和死亡的主要原因。尽管 CF 患者的免疫系统没有明显的原发性缺陷，但宿主通常无法从气道中清除铜绿假单胞菌。PTX3 是一种可溶性模式识别受体，在宿主对真菌、细菌和病毒的固有免疫反应中发挥非冗余作用。特别是，PTX3 缺乏与对铜绿假单胞菌肺部感染的易感性增加有关。为了研究 PTX3 在铜绿假单胞菌肺部感染中的潜在治疗作用，我们使用从 CF 患者中分离的 RP73 临床株 RP73 在小鼠中建立了持续性和进行性感染，并使用重组人 PTX3 进行了治疗。结果表明，PTX3 通过减少肺部定植、促炎细胞因子（CXCL1、CXCL2、CCL2 和 IL-1β）水平和气道中的白细胞募集，对铜绿假单胞菌慢性肺部感染具有潜在的治疗作用。在急性感染模型和体外检测中，PTX3 的促吞噬作用在 C1q 缺陷型小鼠中得以维持，而在 C3 和 Fc 共同γ链缺陷型小鼠中丧失，这表明补体和 FcγRs 之间的相互作用有助于病原体的识别和吞噬，从而介导了 PTX3 的治疗作用。这些数据表明，PTX3 是 CF 患者等慢性铜绿假单胞菌肺部感染的一种潜在治疗工具。
