Rapamycin increases RSV RNA levels and survival of RSV-infected dendritic cell depending on T cell contact. (October 2016)

• Record Type: Journal Article
• Authors: do Nascimento de Freitas, Deise; Gassen, Rodrigo Benedetti; Fazolo, Tiago; Souza, Ana Paula Duarte de
• Is Part Of: Toxicology in vitro. Volume 36(2016)
• Page Start: 114
• Page End: 119
• Publication Date: 2016-10
• Subjects: RSV respiratory syncytial virus -- BMDC bone marrow derived dendritic cells -- DC dendritic cells -- mTOR mechanist target of rapamycin; Respiratory syncytial virus -- Rapamycin -- Dendritic cells -- CD8 T cells; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.07.016
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The macrolide rapamycin inhibits mTOR (mechanist target of rapamycin) function and has been broadly used to unveil the role of mTOR in immune responses. Inhibition of mTOR on dendritic cells (DC) can influence cellular immune response and the survival of DC. RSV is the most common cause of hospitalization in infants and is a high priority candidate to vaccine development. In this study we showed that rapamycin treatment on RSV-infected murine bone marrow-derived DC (BMDC) decreases the frequency of CD8 + CD44 high T cells. However, inhibition of mTOR on RSV-infected BMDC did not modify the activation phenotype of these cells. RSV-RNA levels increase when infected BMDC were treated with rapamycin. Moreover, we observed that rapamycin diminishes apoptosis cell death of RSV-infected BMDC co-culture with T cells and this effect was abolished when the cells were co-cultured in a transwell system that prevents cell-to-cell contact or migration. Taken together, these data indicate that rapamycin treatment present a toxic effect on RSV-infected BMDC increasing RSV-RNA levels, affecting partially CD8 T cell differentiation and also increasing BMDC survival in a mechanism dependent on T cell contact. Graphical abstract: Highlights: Rapamycin treatment on RSV-infected DC decreases CD8 + CD44 high T cells Rapamycin increases RSV Protein F RNA levels on RSV-infected DC. Rapamycin decreases apoptosis of RSV-infected DC depending on T cell contact.