Open AccessFriend virus limits adaptive cellular immune responses by imprinting a maturation-resistant and T helper type 2-biased immunophenotype in dendritic cells
Author(s) -
Limei Shen,
Stefan Tenzer,
Moritz Hess,
Ute Distler,
Ingrid Tubbe,
Evelyn Montermann,
Simone Schimmer,
Ulf Dittmer,
Stephan Grabbe,
Matthias Bros
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0192541
Subject(s) - biology , immune system , immunophenotyping , dendritic cell , antigen presentation , t cell , cd8 , acquired immune system , microbiology and biotechnology , virology , immunology , antigen
The murine Friend virus (FV) retrovirus model has been widely used to study anti-viral immune responses, and virus-induced cancer. Here we analyzed FV immune evasion mechanisms on the level of dendritic cells (DC) essential for the induction of primary adaptive immune responses. Comparative quantitative proteome analysis of FV-infected DC (FV-DC) of different genotypes (BALB/c, C57BL/6) and non-infected DC revealed numerous genotype-independently regulated proteins rergulating metabolic activity, cytoskeletal rearrangements, and antigen processing/presentation. These alterations may promote virion production in FV-DC. Stimulation of FV-DC with LPS resulted in strongly enhanced IL-10 production which was partially responsible for their attenuated T cell (CD4 + , CD8 + ) stimulatory capacity. Stimulated FV-DC induced less IFN-γ production in T cells required for cellular anti-viral responses, but more T helper cell type 2 (Th2)-associated cytokines (IL-4, IL-5, IL-13). We conclude that FV reprograms DC to promote viral spreading and immune deviation by imprinting a largely maturation-resistant, Th2-biased immunophenotype.