title: STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells.
abstract: Kaposis's sarcoma associated herpesvirus (KSHV) has been reported to infect, among others, monocytes and dendritic cells DCs impairing their function. However, the underlying mechanisms remain not completely elucidated yet. Here we show that DC exposure to active or UV-inactivated KSHV resulted in STAT3 phosphorylation. This effect, partially dependent on KSHV-engagement of DC-SIGN, induced a high release of IL-10, IL-6 and IL-23, cytokines that in turn might maintain STAT3 in a phosphorylated state. STAT3 activation also correlated with a block of autophagy in DCs, as indicated by LC3II reduction and p62 accumulation. The IL-10, IL-6 and IL-23 release and the autophagic block could be overcome by inhibiting STAT3 activation, highlighting the role of STAT3 in mediating such effects. In conclusion, here we show that STAT3 activation can be one of the molecular mechanisms leading to KSHV-mediated DC dysfunction, that might allow viral persistence and the onset of KSHV-associated malignancies.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Santarelli
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gonnella
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Di Giovenale
authors.affiliation: Department of Clinical Pathology, A.C.O., S. Filippo Neri, Via Giovanni Martinotti, 20, 00135 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cuomo
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161 Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Capobianchi
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Granato
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gentile
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: C508609:IL10 protein, human; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10