Yano Tamaki, Mita Shizuka, Ohmori Hiroko, Oshima Yoshiteru, Fujimoto Yukari, Ueda Ryu, Takada Haruhiko, Goldman William E, Fukase Koichi, Silverman Neal, Yoshimori Tamotsu, Kurata Shoichiro
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Nat Immunol. 2008 Aug;9(8):908-16. doi: 10.1038/ni.1634. Epub 2008 Jul 6.
Autophagy, an evolutionally conserved homeostatic process for catabolizing cytoplasmic components, has been linked to the elimination of intracellular pathogens during mammalian innate immune responses. However, the mechanisms underlying cytoplasmic infection-induced autophagy and the function of autophagy in host survival after infection with intracellular pathogens remain unknown. Here we report that in drosophila, recognition of diaminopimelic acid-type peptidoglycan by the pattern-recognition receptor PGRP-LE was crucial for the induction of autophagy and that autophagy prevented the intracellular growth of Listeria monocytogenes and promoted host survival after this infection. Autophagy induction occurred independently of the Toll and IMD innate signaling pathways. Our findings define a pathway leading from the intracellular pattern-recognition receptors to the induction of autophagy to host defense.
自噬是一种进化上保守的分解细胞质成分的稳态过程,在哺乳动物先天免疫反应期间,它与细胞内病原体的清除有关。然而,细胞质感染诱导自噬的潜在机制以及自噬在细胞内病原体感染后宿主存活中的作用仍不清楚。在此,我们报道在果蝇中,模式识别受体PGRP-LE对二氨基庚二酸型肽聚糖的识别对于自噬的诱导至关重要,并且自噬可防止单核细胞增生李斯特菌在细胞内生长,并促进感染后宿主的存活。自噬诱导独立于Toll和IMD先天信号通路发生。我们的研究结果定义了一条从细胞内模式识别受体到自噬诱导再到宿主防御的途径。