Dendritic cell maturation by proinflammatory TNF or pathogenic Trypanosoma brucei antigens instruct similar T helper-2 cell responses in murine models of autoimmunity and asthma. Mus musculus

Background Dendritic cells (DC) represent the major cell type leading to polarized T helper (Th) cell responses in vivo. The current data indicate that DC maturation under inflammatory conditions or by helminth infections induce only incomplete DC maturation bearing a partially tolerogenic potential. Such semi-mature DC promoted a Th2 profile with increasing proportions of regulatory IL-10 producing T cells (Tr-1) upon restimulation. Methodology/Principal Findings Here we asked whether the instruction of DC by the proinflammatory cytokine TNF is qualitatively different from maturation by two types of variant surface glycoproteins (VSGs) of Trypanosoma brucei. We tested differentially matured murine bone marrow (BM)-derived DC for changes in surface markers or cytokines, by microarray analyses, for their induction of Th2 responses and their capacity to influence the disease models asthma for Th2 immunity and experimental autoimmune encephalomyelitis (EAE) for a Th1/Th17 response. Conclusions/Significance Together, our data suggest that the partial maturation signatures induced by TNF and VSG antigens are highly similar and result in comparable Th2/Tr1 profiles, effects on asthma and EAE. This is remarkable since the responses resulting from endogenous inflammatory TNF-receptor signals or exogenous pathogenic MyD88 ligands are comparable. Overall design: total samples analysed are 5