IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Rab22a is a critical regulator of Toxoplasma gondii proliferation in dendritic cells
Autor/es:
FACUNDO GARRIDO; NICOLAS BLANCHARD; CRISTINA CROCE; IGNACIO CEBRIÁN; SOFÍA DINAMARCA; LUIS MAYORGA
Lugar:
Mendoza
Reunión:
Congreso; LVI SAIB Meeting - XV SAMIGE Meeting; 2020
Institución organizadora:
SAIB-SAMIGE
Resumen:
Toxoplasma gondii is an obligate intracellular protozoan parasite of the phylum Apicomplexa. This microorganism has developed multiple strategies to infect almost all nucleated warm blood animal cells including dendritic cells (DCs), the most efficient antigen presenting cell type. Also, this parasite is the causative agent responsible of toxoplasmosis, one of the most widespread zoonotic diseases. In order to survive, T. gondii has to successfully achieve cell invasion and replication. Once inside the host cell, the parasite secretes different moving junction proteins in a tightly regulated fashion and builds the parasitophorous vacuole (PV), the niche for replication and survival in the cytoplasm. Multiple interactions between the PV and host cell organelles have been described. However, the molecular effectors involved in this connection and the outcome for the parasite growth and survival are still mostly unknown. In a previous work, our group has identified the small GTPase Rab22a as a critical regulator of cross-presentation, including T. gondii-derived antigens. Furthermore, Rab22a regulates MHC-I molecules recycling and the delivery of these molecules to DC phagosomes. Although Rab22a is recruited to the PV of T. gondii very early after infection, is not essential for effective invasion. In this study, we aim to address the role of Rab22a at later stages of DC infection by T. gondii. In this sense, we have observed by immunofluorescence and confocal microscopy that Rab22a strongly localizes around the PV at 24, 48 and 72 hours post-infection. Moreover, by silencing the expression of Rab22a in DCs with shRNAs (Rab22a KD), we studied the proliferative capacity of T. gondii within these cells and control cells (Scramble). By using a fluorescent strain of the parasite and a flow cytometry-based approach, we determined that T. gondii is not able to replicate properly after 24 hours post-infection, suggesting an important role for Rab22a in late stages of the infection. Ongoing experiments will help us to understand this novel function of Rab22a in the context of T. gondii infection.