清道夫受体SCARF1和CD36对真菌病原体的进化保守识别及固有免疫

Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36.

作者信息

Means Terry K, Mylonakis Eleftherios, Tampakakis Emmanouil, Colvin Richard A, Seung Edward, Puckett Lindsay, Tai Melissa F, Stewart Cameron R, Pukkila-Worley Read, Hickman Suzanne E, Moore Kathryn J, Calderwood Stephen B, Hacohen Nir, Luster Andrew D, El Khoury Joseph

机构信息

Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

出版信息

J Exp Med. 2009 Mar 16;206(3):637-53. doi: 10.1084/jem.20082109. Epub 2009 Feb 23.

Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was beta-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are beta-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens.

参与对真菌病原体固有免疫的受体尚未完全阐明。我们发现，秀丽隐杆线虫受体CED-1和C03F11.3，以及它们在哺乳动物中的同源物，即清道夫受体SCARF1和CD36，介导宿主对两种典型真菌病原体新型隐球菌和白色念珠菌的防御。CED-1和C03F11.1介导抗菌肽的产生，并且是新型隐球菌感染后线虫存活所必需的。SCARF1和CD36介导细胞因子的产生，并且是巨噬细胞结合新型隐球菌以及控制小鼠感染所必需的。这些病原体与SCARF1和CD36的结合是β-葡聚糖依赖性的。因此，CED-1/SCARF1和C03F11.3/CD36是β-葡聚糖结合受体，并定义了一条用于真菌病原体固有感知的进化保守途径。