当前位置: X-MOL 学术Cell Host Microbe › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.chom.2020.09.004
Johannes Westman 1 , Glenn F W Walpole 2 , Lydia Kasper 3 , Bessie Y Xue 4 , Osama Elshafee 3 , Bernhard Hube 5 , Sergio Grinstein 6
Affiliation  

Phagosomes must maintain membrane integrity to exert their microbicidal function. Some microorganisms, however, survive and grow within phagosomes. In such instances, phagosomes must expand to avoid rupture and microbial escape. We studied whether phagosomes regulate their size to preserve integrity during infection with the fungal pathogen Candida albicans. Phagosomes release calcium as C. albicans hyphae elongate, inducing lysosome recruitment and insertion, thereby increasing the phagosomal surface area. As hyphae grow, the expanding phagosome consumes the majority of free lysosomes. Simultaneously, lysosome biosynthesis is stimulated by activation of TFEB, a transcriptional regulator of lysosomal biogenesis. Preventing lysosomal insertion causes phagosomal rupture, NLRP3 inflammasome activation, IL-1β secretion and host-cell death. Whole-genome transcriptomic analysis demonstrate that stress responses elicited in C. albicans upon engulfment are reversed if phagosome expansion is prevented. Our findings reveal a mechanism whereby phagosomes maintain integrity while expanding, ensuring that growing pathogens remain entrapped within this microbicidal compartment.



中文翻译:

溶酶体融合在真菌感染过程中保持吞噬体完整性。

吞噬体必须保持膜的完整性才能发挥其杀微生物功能。但是,某些微生物可以在吞噬体内存活并生长。在这种情况下,吞噬体必须扩展以避免破裂和微生物逸出。我们研究了吞噬体是否在真菌病原体白色念珠菌感染期间调节大小以保持完整性。吞噬体释放钙作为Ç白色的菌丝伸长,诱导溶酶体募集和插入,从而增加了吞噬体的表面积。随着菌丝的生长,膨胀的吞噬体会消耗掉大部分的游离溶酶体。同时,通过溶酶体生物发生的转录调节因子TFEB的激活来刺激溶酶体的生物合成。防止溶酶体插入会导致吞噬体破裂,NLRP3炎性体激活,IL-1β分泌和宿主细胞死亡。全基因组转录组学分析表明应激反应在C中引起。如果阻止吞噬体膨胀,吞噬时的白色念珠菌将逆转。我们的发现揭示了吞噬体在扩张的同时保持完整性的机制,从而确保了不断增长的病原体仍被截留在该杀菌室中。

更新日期:2020-12-09
down
wechat
bug