Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
J Exp Med. 2010 Dec 20;207(13):2907-19. doi: 10.1084/jem.20100034. Epub 2010 Dec 13.
Host defense against opportunistic fungi requires coordination between innate and adaptive immunity for resolution of infection. Antibodies generated in mice vaccinated with the fungus Pneumocystis prevent growth of Pneumocystis organisms within the lungs, but the mechanisms whereby antibodies enhance antifungal host defense are poorly defined. Nearly all species of fungi contain the conserved carbohydrates β-glucan and chitin within their cell walls, which may be targets of innate and adaptive immunity. In this study, we show that natural IgM antibodies targeting these fungal cell wall carbohydrates are conserved across many species, including fish and mammals. Natural antibodies bind fungal organisms and enhance host defense against Pneumocystis in early stages of infection. IgM antibodies influence recognition of fungal antigen by dendritic cells, increasing their migration to draining pulmonary lymph nodes. IgM antibodies are required for adaptive T helper type 2 (Th2) and Th17 cell differentiation and guide B cell isotype class-switch recombination during host defense against Pneumocystis. These experiments suggest a novel role for the IgM isotype in shaping the earliest steps in recognition and clearance of this fungus. We outline a mechanism whereby serum IgM, containing ancient specificities against conserved fungal antigens, bridges innate and adaptive immunity against fungal organisms.
宿主防御机会性真菌需要先天免疫和适应性免疫之间的协调，以解决感染。用真菌肺囊虫(Pneumocystis) 疫苗接种的小鼠产生的抗体可防止肺内肺囊虫生物的生长，但抗体增强抗真菌宿主防御的机制尚未明确。几乎所有真菌物种的细胞壁中都含有保守的碳水化合物β-葡聚糖和几丁质，它们可能是先天免疫和适应性免疫的靶点。在这项研究中，我们表明，针对这些真菌细胞壁碳水化合物的天然 IgM 抗体在包括鱼类和哺乳动物在内的许多物种中是保守的。天然抗体结合真菌生物，增强宿主对感染早期肺囊虫的防御。IgM 抗体影响树突状细胞对真菌抗原的识别，增加它们向引流肺淋巴结的迁移。IgM 抗体是宿主防御肺囊虫所必需的适应性 T 辅助细胞 2(Th2)和 Th17 细胞分化，并指导 B 细胞同种型类别转换重组。这些实验表明 IgM 同种型在塑造识别和清除这种真菌的最早步骤中具有新的作用。我们概述了一种机制，即含有针对保守真菌抗原的古老特异性的血清 IgM，可桥连先天免疫和适应性免疫以抵抗真菌生物。
