Endogenously produced TNF- alpha contributes to the expression of CXCL10/IP-10 in IFN- lambda 3-activated plasmacytoid dendritic cells

• Published in: Journal of leukocyte biology Vol. 99; no. 1; pp. 107 - 119
• Main Authors: Finotti, Giulia, Tamassia, Nicola, Calzetti, Federica, Fattovich, Giovanna, Cassatella, Marco A
• Format: Journal Article
• Language: English
• Published: 17.01.2016
• Subjects: Hepatitis C virus
• ISSN: 0741-5400
• DOI: 10.1189/jlb.3VMA0415-144R

Human plasmacytoid dendritic cells respond to IFN- lambda in terms of prolonged survival, partial maturation, and production of IFN- alpha , CXCL10, and TNF- alpha . The interplay between IFN- lambda s and dendritic cells is becoming increasingly relevant, particularly in light of their key role in inducing the antiviral state, including in hepatitis C virus infection. In this work, we have analyzed extensively how human plasmacytoid dendritic cells respond to IFN- lambda 3. We report that plasmacytoid dendritic cells incubated with IFN- lambda 3 prolong their survival; alter their expression pattern of surface HLA-DR alpha , CD123, CD86, and CD303; and time dependently produce IFN- alpha , CXCL10/IFN- gamma -induced protein 10, and even modest quantities of TNF- alpha . Nevertheless, endogenously produced TNF- alpha , but not IFN- alpha , was found to be essential for driving the expression of CXCL10/IFN- gamma -induced protein 10 in IFN- lambda 3-treated plasmacytoid dendritic cells, as revealed by neutralizing experiments by use of adalimumab, etanercept, and infliximab. We also observed that based on the kinetics and levels of IFN- alpha and CXCL10/IFN- gamma -induced protein 10 produced by their IFN- lambda 3-treated plasmacytoid dendritic cells, healthy donors could be categorized into 2 and 3 groups, respectively. In particular, we identified a group of donors whose plasmacytoid dendritic cells produced modest quantities of CXCL10/IFN- gamma -induced protein 10; another one whose plasmacytoid dendritic cells produced elevated CXCL10/IFN- gamma -induced protein 10 levels, already after 18 h, declining thereafter; and a 3rd group characterized by plasmacytoid dendritic cells releasing very high CXCL10/IFN- gamma -induced protein 10 levels after 42 h only. Finally, we report that in plasmacytoid dendritic cells, equivalent concentrations of IFN- lambda 3 and IFN- lambda 1 promote survival, antigen modulation, and cytokine production in a comparable manner and without acting additively/synergistically. Altogether, data not only extend the knowledge on the biologic effects that IFN- lambda s exert on plasmacytoid dendritic cells but also add novel light to the networking between IFN- lambda s and plasmacytoid dendritic cells in fighting viral diseases.