Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner
Tropheryma whipplei, the agent of Whipple’s disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of T. whipplei replicative vacuole remain poorly understood. Macrophage microbicidal activity is largely related to macro/a...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2025.2475527 |
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| author | Emilie Reyne Jeffrey Arrindell Eloïne Bestion Soraya Mezouar Benoit Desnues |
| author_facet | Emilie Reyne Jeffrey Arrindell Eloïne Bestion Soraya Mezouar Benoit Desnues |
| author_sort | Emilie Reyne |
| collection | DOAJ |
| description | Tropheryma whipplei, the agent of Whipple’s disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of T. whipplei 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 T. whipplei 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 T. whipplei 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 T. whipplei infection. |
| format | Article |
| id | doaj-art-cf873125922f47528d84fc9446fbbf54 |
| institution | DOAJ |
| issn | 2769-4127 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-cf873125922f47528d84fc9446fbbf542025-08-20T03:05:52ZengTaylor & Francis GroupAutophagy Reports2769-41272025-12-014110.1080/27694127.2025.2475527Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent mannerEmilie Reyne0Jeffrey Arrindell1Eloïne Bestion2Soraya Mezouar3Benoit Desnues4Aix-Marseille Univ, MEPHI, Marseille, FranceAix-Marseille Univ, MEPHI, Marseille, FranceGenoscience Pharma, 13006 Marseille, FranceAix-Marseille Univ, ADES, CNRS, EFS, Marseille, FranceAix-Marseille Univ, MEPHI, Marseille, FranceTropheryma whipplei, the agent of Whipple’s disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of T. whipplei 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 T. whipplei 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 T. whipplei 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 T. whipplei infection.https://www.tandfonline.com/doi/10.1080/27694127.2025.2475527AutophagyImmune escapeLC3-associated phagocytosis (LAP)MacrophageTropheryma whippleiWhipple’s disease |
| spellingShingle | Emilie Reyne Jeffrey Arrindell Eloïne Bestion Soraya Mezouar Benoit Desnues Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner Autophagy Reports Autophagy Immune escape LC3-associated phagocytosis (LAP) Macrophage Tropheryma whipplei Whipple’s disease |
| title | Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner |
| title_full | Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner |
| title_fullStr | Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner |
| title_full_unstemmed | Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner |
| title_short | Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner |
| title_sort | tropheryma whipplei escapes laposome and modulates macrophage response in a xenophagy dependent manner |
| topic | Autophagy Immune escape LC3-associated phagocytosis (LAP) Macrophage Tropheryma whipplei Whipple’s disease |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2025.2475527 |
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