A noncanonical autophagy is involved in the transfer of Plasmodium -microvesicles to astrocytes
| Autor: | Sophie Salomé Desnoulez, Priscille Brodin, Sylviane Pied, Nasreddine Saidi, Frank Lafont, Inès Leleu, Stanislas Tomavo, Delphine Genete |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Pied, Sylviane, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Biologie Intégrative de la Cellule [I2BC] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Plasmodium
autophagy Plasmodium berghei [SDV]Life Sciences [q-bio] ATG5 Malaria Cerebral Inflammation Biology parasite microvesicles Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine parasitic diseases medicine Animals [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Innate immune system Autophagy Cell Biology Astrocyte cerebral malaria inflammation Microvesicles 3. Good health Cell biology Mice Inbred C57BL [SDV] Life Sciences [q-bio] medicine.anatomical_structure Cerebral Malaria Astrocytes medicine.symptom 030217 neurology & neurosurgery [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Research Paper |
| Zdroj: | Autophagy Autophagy, Taylor & Francis, 2021, pp.1-16. ⟨10.1080/15548627.2021.1993704⟩ Autophagy, 2022, 18 (7), pp.1583-1598. ⟨10.1080/15548627.2021.1993704⟩ |
| ISSN: | 1554-8627 1554-8635 |
| DOI: | 10.1080/15548627.2021.1993704⟩ |
| Popis: | International audience; Cerebral malaria is a neuroinflammatory disease induced by P. falciparum infection. In animal models, the neuro-pathophysiology of cerebral malaria results from the sequestration of infected red blood cells (iRBCs) in microvessels that promotes the activation of glial cells in the brain. This activation provokes an exacerbated inflammatory response characterized by the secretion of proinflammatory cytokines and chemokines, leading to brain infiltration by pathogenic CD8+ T lymphocytes. Astrocytes are a major subtype of brain glial cells that play an important role in maintaining the homeostasis of the central nervous system, the integrity of the brain-blood barrier and in mounting local innate immune responses. We have previously shown that parasitic microvesicles (PbA-MVs) are transferred from iRBCs to astrocytes. The present study shows that an unconventional LC3-mediated autophagy pathway independent of ULK1 is involved in the transfer and degradation of PbA-MVs inside the astrocytes. We further demonstrate that inhibition of the autophagy process by treatment with 3-methyladenine blocks the transfer of PbA-MVs, which remain localized in the astrocytic cell membrane and are not internalized. Moreover, bafilomycin A1, another drug against autophagy promotes the accumulation of PbA-MVs inside the astrocytes by inhibiting the fusion with lysosomes, and prevents ECM in mice infected with PbA. Finally, we establish that RUBCN/rubicon or ATG5 silencing impede astrocyte production in CCL2 and CXCL10 chemokines induced by PbA stimulation. Altogether, our data suggest that a non-canonical autophagy-lysosomal pathway may play a key role in cerebral malaria through regulation of brain neuro-inflammation by astrocytes. |
| Databáze: | OpenAIRE |
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