L’infection au VIH-1 augmente l’accumulation des vésicules extracellulaires libérées par les cellules RAJI CD4 DCIR mises en contact avec le VIH-1. Ceci est conforté avec l’observation chez les patients infectés au VIH-1 montrant une abondance des exosomes issus des plasmas des patients infectés en comparaison avec les sujets non infectés.
Nous avons mis au point l’immunobuvardage avec l’anti-Dap-3 qui permet d’augmenter le signal de marquage tout en réduisant le cout de la technique. De plus, nous avons montré que la protéine pro-apoptotique Dap-3 est présente dans les vésicules extracellulaires issues des cellules RAJI CD4 DCIR infectées au VIH-1 en comparaison avec les cellules non infectées. Également, Dap-3 est plus présent dans les exosomes issus des cellules RAJI CD4 DCIR infectées au VIH-1 en comparaison avec celles des cellules non infectées. Cependant, la protéine Dap-3 est plus présente dans les dernières fractions du gradient de vélocité issues des cellules infectées au VIH-1 et que ces fractions contiennent peut-être des vésicules apoptotiques. Une caractérisation de ces fractions du gradient est requise afin de déterminer la présence de vésicules apoptotiques ou d’autres types de vésicules pas encore identifiées.
L’ultracentrifugation des vésicules extracellulaires sur les gradients de vélocité permet la séparation de plusieurs populations de vésicules avec des tailles différentes analysées avec le nanosizer. Les fractions du gradient de vélocité sont à caractériser par microscopie électronique et immunobuvardage des marqueurs d’exosomes afin de visualiser les différents types de vésicules.
Afin de montrer le rôle de Dap-3 dans l’apoptose des LT CD4 par les exosomes, il serait pertinent de récupérer les vésicules extracellulaires Dap-3- à partir des cellules dendritiques
transfectées avec l’ARN anti-sens Dap-3 et infectées au VIH-1. Et ce, dans le but d’analyser le rôle de ces vésicules Dap-3- dans l’apoptose des LT CD4 en comparaison
avec les vésicules Dap-3+. Ceci nous permettra de savoir si la protéine Dap-3 représente un
mécanisme par lequel les exosomes issus des cellules infectées activent l’apoptose des LT CD4.
62
À plus long terme, une analyse quantitative de Dap-3 par ELISA sur les LT CD4 issus des PBMCs des patients VIH-1+ ainsi que sur les vésicules extracellulaires issues des plasmas
des patients VIH-1+ pourrait peut-être servir au pronostique de mortalité des LT CD4. En
effet, l’étude de la corrélation entre la quantité de Dap-3 et l’apoptose des LT CD4 permettra de montrer le rôle de Dap-3 dans la pathogenèse de l’infection au VIH-1 ou comme outil de pronostique. Enfin, il est possible que les vésicules extracellulaires issues des cellules infectées au VIH-1 contiennent d’autres molécules pro-apoptotiques comme les récepteurs de mort cellulaire PD-L1, Fas-L et Fas dont il serait pertinent de valider la présence dans les vésicules extracellulaires.
63
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