Joubert Pierre-Emmanuel, Meiffren Grégory, Grégoire Isabel Pombo, Pontini Guillemette, Richetta Clémence, Flacher Monique, Azocar Olga, Vidalain Pierre-Olivier, Vidal Marc, Lotteau Vincent, Codogno Patrice, Rabourdin-Combe Chantal, Faure Mathias
Université de Lyon, Lyon, F-69003, France.
Cell Host Microbe. 2009 Oct 22;6(4):354-66. doi: 10.1016/j.chom.2009.09.006.
Autophagy is a highly regulated self-degradative mechanism required at a basal level for intracellular clearance and recycling of cytoplasmic contents. Upon intracellular pathogen invasion, autophagy can be induced as an innate immune mechanism to control infection. Nevertheless, pathogens have developed strategies to avoid or hijack autophagy for their own benefit. The molecular pathways inducing autophagy in response to infection remain poorly documented. We report here that the engagement of CD46, a ubiquitous human surface receptor able to bind several different pathogens, is sufficient to induce autophagy. CD46-Cyt-1, one of the two C-terminal splice variants of CD46, is linked to the autophagosome formation complex VPS34/Beclin1 via its interaction with the scaffold protein GOPC. Measles virus and group A Streptococcus, two CD46-binding pathogens, induce autophagy through a CD46-Cyt-1/GOPC pathway. Thus, upon microorganism recognition, a cell surface pathogen receptor can directly trigger autophagy, a critical step to control infection.
自噬是一种高度调控的自我降解机制，在基础水平上是细胞内清除和细胞质内容物循环所必需的。在细胞内病原体入侵时，自噬可作为一种先天性免疫机制被诱导以控制感染。然而，病原体已发展出策略以避免或劫持自噬来为自身谋利。响应感染诱导自噬的分子途径仍记录甚少。我们在此报告，CD46（一种能够结合多种不同病原体的普遍存在的人类表面受体）的激活足以诱导自噬。CD46-Cyt-1是CD46的两个C末端剪接变体之一，它通过与支架蛋白GOPC相互作用与自噬体形成复合物VPS34/Beclin1相连。麻疹病毒和A组链球菌这两种结合CD46的病原体，通过CD46-Cyt-1/GOPC途径诱导自噬。因此，在识别微生物时，细胞表面病原体受体可直接触发自噬，这是控制感染的关键步骤。
