Gonzalez-Suarez Maria L, Salinas-Carmona Mario C, Pérez-Rivera Isabel
Department of Immunology, Faculty of Medicine and University Hospital, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
FEMS Immunol Med Microbiol. 2009 Oct;57(1):17-24. doi: 10.1111/j.1574-695X.2009.00575.x. Epub 2009 Jun 10.
Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.
巴西诺卡菌是一种兼性胞内微生物,可引发一种名为放线菌性足菌肿的人类慢性感染。人和小鼠的抗巴西诺卡菌抗体反应可识别P24、P26和P61免疫显性抗原。在本研究中,我们制备了针对免疫显性P61抗原的免疫球蛋白M(IgM)和IgG单克隆抗体(mAb)。对单克隆IgM(NbM1)和IgG2a(NbG1)抗体的体外杀菌活性、体内保护作用及阻断过氧化氢酶活性的能力进行了评估。这些单克隆抗体可特异性识别P61,但不抑制其酶活性。NbG1的体外杀菌效果高于IgM单克隆抗体的杀伤能力。采用将巴西诺卡菌注射到后足垫的小鼠实验性感染模型进行体内实验,以测试NbM1和NbG1的效果。未处理的阴性对照组在4周内形成了慢性放线菌性足菌肿。IgM单克隆抗体对感染巴西诺卡菌的BALB/c小鼠具有保护作用。IgG单克隆抗体缺乏这种保护作用。IgM单克隆抗体在抗体浓度与病变大小之间呈现剂量反应相关性。这些结果表明,抗原特异性IgM抗体介导的体液免疫反应可抵御细胞内细菌感染。