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Histamine releasing factor and elongation factor 1 alpha secreted via malaria parasites extracellular vesicles promote immune evasion by inhibiting specific T cell responses

Abstract : Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmo-dium berghei NK65 blood stage-derived EVs of the proliferative response of CD4 + T cells in response to antigen presentation. Importantly, these results were confirmed in vivo by the capacity of EVs to diminish the ovalbumin-specific delayed type hyper-sensitivity response. We identified two proteins associated with EVs, the histamine releasing factor (HRF) and the elongation factor 1α (EF-1α) that were found to have immunosuppressive activities. Interestingly, in contrast to WT parasites, EVs from genetically HRF-and EF-1α-deficient parasites failed to inhibit T cell responses in vitro and in vivo. At the level of T cells, we demonstrated that EVs from WT parasites dephosphorylate key molecules (PLCγ1, Akt, and ERK) of the T cell receptor signalling cascade. Remarkably, immunisation with EF-1α alone or in combination with HRF conferred a long-lasting antiparasite protection and immune memory. In conclusion, we identified a new mechanism by which P. berghei-derived EVs exert their immunosuppressive functions by altering T cell responses. The identification of two highly conserved immune suppressive factors offers new conceptual strategies to overcome EV-mediated immune suppression in malaria-infected individuals.
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https://hal.univ-angers.fr/hal-02571995
Contributeur : Salah Mecheri <>
Soumis le : vendredi 29 mai 2020 - 09:44:38
Dernière modification le : mardi 4 août 2020 - 17:40:05

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HRF-EF-1-Exosome-Malaria.pdf
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Claudia Demarta-Gatsi, Anna Rivkin, Vincenzo Di Bartolo, Roger Peronet, Shuai Ding, et al.. Histamine releasing factor and elongation factor 1 alpha secreted via malaria parasites extracellular vesicles promote immune evasion by inhibiting specific T cell responses. Cellular Microbiology, Wiley, 2019, 21 (7), ⟨10.1111/cmi.13021⟩. ⟨hal-02571995v2⟩

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