耶氏肺孢子菌与宿主免疫防御相互作用

Interaction between Pneumocystis jirovecii and host immune defense

肺孢子菌肺炎(Pneumocystis pneumonia,PCP)是由酵母样真菌耶氏肺孢子菌(Pneumocystis jirovecii,Pj)引起的肺炎,是免疫缺陷患者重要的致死原因。Pj一般不导致系统性感染,仅在肺部繁殖,引发严重损害肺换气功能的间质性肺炎。Pj通过主要表面糖蛋白(major surface glycoprotein,MSG)的抗原转换,逃避宿主免疫系统清除,而宿主利用dectin-1识别β-(1,3)-D-葡聚糖(beta-1,3-D-glucan,BG)、甘露糖受体识别MSG,启动天然免疫反应,继而CD4+T细胞聚集活化,调控细胞免疫和体液免疫。分泌干扰素γ的细胞毒型CD8+Tc1细胞有助于控制Pj感染,特异性抗体有助于调理加强吞噬细胞清除Pj,而聚集的中性粒细胞和非Tc1CD8+T细胞与肺损伤有关。血浆BG水平可以辅助诊断PCP,而支气管肺泡灌洗液中白介素8的水平与肺损伤及死亡预后有关。

Pneumocystis pneumonia （PCP） is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii （Pj）. It is an important lethal factor in immunodeficient patients. Pj generally does not cause systemic infection, only multiply in the lungs. Interstitial pneumonia caused by Pj seriously damages the oxygen exchange function of the lung. Pj uses major surface glyco- protein （MSG） antigen switch to escape host immune elimination. The host initiates innate immune response through the interactions of macrophage mannose receptors with the MSG as well as through interaction of macrophage dectin-1 receptors interacting with the beta-1,3-D-glucan （BG） moiety of the organisms. Pattern recognition induces chemokines and inflammatory cytokine production, which promoting neutrophils and T-lymphocytes recruitment and activation. Cytotoxic 1 CD8＋ T cells which producing interferon-γ are critical in helping control of Pj infections. IgG may facilitate the uptake process by opsonization of the organisms. Neutrophil and non Tcl CD8 ＋T cell recruitment seems to closely correlate with lung injury in humans. The level of BG can help diagnosing PCP. The level of interleukin-8 in the bronchoalveolar lavage fluid could be a predictor of lung impairment and death from PCP.