Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection
Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection
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DOI：
10.1073/pnas.1405032111
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发表时间：
2014-08-26
影响因子：
11.1
通讯作者：
Zhang, Ke-Qin
中科院分区：
文献类型：
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作者：
Zou, Cheng-Gang;Ma, Yi-Cheng;Zhang, Ke-Qin
自噬是一种将细胞内物质输送到溶酶体进行降解的保守途径，与发育、衰老和多种疾病有关。越来越多的证据表明，自噬通过减少细胞内病原体（包括细菌、病毒和寄生虫）来对抗传染病。然而，自噬调节先天免疫的机制仍然很大程度上未知。在这里，我们发现自噬参与了宿主对后生动物秀丽隐杆线虫中致病菌铜绿假单胞菌的防御。铜绿假单胞菌感染通过保守的细胞外信号调节激酶 (ERK) 诱导自噬。有趣的是，自噬受损并不影响铜绿假单胞菌在肠道内的积累，反而会诱导肠道坏死。坏死的抑制导致自噬缺陷的蠕虫在铜绿假单胞菌感染后存活。这些发现揭示了自噬在防止秀丽隐杆线虫病原菌引起的坏死方面先前未确定的作用，并暗示自噬的这种功能可能通过多种生物体的炎症反应而得以保留。
Autophagy, a conserved pathway that delivers intracellular materials into lysosomes for degradation, is involved in development, aging, and a variety of diseases. Accumulating evidence demonstrates that autophagy plays a protective role against infectious diseases by diminishing intracellular pathogens, including bacteria, viruses, and parasites. However, the mechanism by which autophagy regulates innate immunity remains largely unknown. Here, we show that autophagy is involved in host defense against a pathogenic bacterium Pseudomonas aeruginosa in the metazoan Caenorhabditis elegans. P. aeruginosa infection induces autophagy via a conserved extracellular signal-regulated kinase (ERK). Intriguingly, impairment of autophagy does not influence the intestinal accumulation of P. aeruginosa, but instead induces intestinal necrosis. Inhibition of necrosis results in the survival of autophagy-deficient worms after P. aeruginosa infection. These findings reveal a previously unidentified role for autophagy in protection against necrosis triggered by pathogenic bacteria in C. elegans and implicate that such a function of autophagy may be conserved through the inflammatory response in diverse organisms.