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逃脱脂质体自噬体(LAPosome)并以自噬依赖性方式调节巨噬细胞反应。

escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner.

作者信息

Reyne Emilie, Arrindell Jeffrey, Bestion Eloïne, Mezouar Soraya, Desnues Benoit

机构信息

Aix-Marseille Univ, MEPHI, Marseille, France.

IHU-Méditerranée Infection, Marseille, France.

出版信息

Autophagy Rep. 2025 Mar 11;4(1):2475527. doi: 10.1080/27694127.2025.2475527. eCollection 2025.

DOI:10.1080/27694127.2025.2475527
PMID:40395986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11921966/
Abstract

, the agent of Whipple's disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of replicative vacuole remain poorly understood. Macrophage microbicidal activity is largely related to macro/autophagy which is also essential for cell homeostasis. Here, we show that uptake by macrophages involved LC3-associated phagocytosis (LAP). Bacteria then escaped into the cytosol from where they were recaptured by xenophagy. We also demonstrate that blocked the autophagic flux to build its replicative compartment. Inhibition of LAP resulted in the decrease of interleukin (IL)-10 secretion and the restoration of the autophagy flux, suggesting that modulation of autophagy during infection alters immune response and promote persistence. Our results provide new insight in the intracellular fate of the bacteria during macrophage infection and suggest the possible involvement of previously unknown virulence factors in infection.

摘要

惠普尔病的病原体是一种在巨噬细胞内复制的细胞内病原体。导致复制性液泡形成的吞噬和细胞过程仍知之甚少。巨噬细胞的杀菌活性在很大程度上与大自噬/自噬有关,而这对细胞稳态也至关重要。在这里,我们表明巨噬细胞对该病原体的摄取涉及LC3相关吞噬作用(LAP)。然后细菌逃入细胞质,在那里它们被异噬作用重新捕获。我们还证明该病原体阻断自噬通量以构建其复制区室。抑制LAP导致白细胞介素(IL)-10分泌减少和自噬通量恢复,这表明感染期间自噬的调节会改变免疫反应并促进病原体持续存在。我们的结果为巨噬细胞感染期间细菌的细胞内命运提供了新的见解,并表明以前未知的毒力因子可能参与该病原体的感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/9a5e149d4da7/KAUO_A_2475527_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/0ca8f1020765/KAUO_A_2475527_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/adc1fd9dc060/KAUO_A_2475527_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/783d692f3bf6/KAUO_A_2475527_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/35080831f72a/KAUO_A_2475527_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/7b148f9af50c/KAUO_A_2475527_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/9a5e149d4da7/KAUO_A_2475527_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/0ca8f1020765/KAUO_A_2475527_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/adc1fd9dc060/KAUO_A_2475527_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/783d692f3bf6/KAUO_A_2475527_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/35080831f72a/KAUO_A_2475527_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/7b148f9af50c/KAUO_A_2475527_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d3/11921966/9a5e149d4da7/KAUO_A_2475527_F0006_OC.jpg

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