title: Rapamycin increases RSV RNA levels and survival of RSV-infected dendritic cell depending on T cell contact.
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.
authors.affiliation: Laboratório de Imunologia Clinica e Experimental; Centro Infant, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Deise
authors.initials: D
authors.lastname: do Nascimento de Freitas
authors.affiliation: Laboratório de Imunologia Clinica e Experimental; Centro Infant, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Laboratório de Imunologia Celular e Molecular, PUCRS, Brazil.
authors.forename: Rodrigo Benedetti
authors.initials: RB
authors.lastname: Gassen
authors.affiliation: Laboratório de Imunologia Clinica e Experimental; Centro Infant, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Laboratório de Imunologia Celular e Molecular, PUCRS, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fazolo
authors.affiliation: Laboratório de Imunologia Clinica e Experimental; Centro Infant, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Faculdade de Farmácia, PUCRS, Brazil. Electronic address: ana.duarte@pucrs.br.
authors.forename: Ana Paula Duarte de
authors.initials: APD
authors.lastname: Souza
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000821:virology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D012367:RNA, Viral; D014764:Viral Proteins; D020123:Sirolimus
keywords: CD8 T cells; Dendritic cells; Rapamycin; Respiratory syncytial virus