Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-gamma
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Publication year
2014Source
International Immunology, 26, 12, (2014), pp. 705-16ISSN
Publication type
Article / Letter to editor
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Organization
Tumorimmunology
Journal title
International Immunology
Volume
vol. 26
Issue
iss. 12
Page start
p. 705
Page end
p. 16
Subject
Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
The capacity to develop protective immunity against mycobacteria is heterogeneously distributed among human beings, and it is currently unknown why the initial immune response induced against Mycobacterium tuberculosis (Mtb) does not provide proper clearance of this pathogen. Dendritic cells (DCs) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN-gamma-producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we report that Mtb modifies human DC plasticity by expanding a CD14+ DC subset with weak IL-12p70-producing capacity. The CD14+ Mtb-promoted subset was furthermore poor inducers of IFN-gamma by naive CD4+ T cells, but instead prompted IL-17A-producing RORgammaT+ CD4+ T cells. Mtb-derived peptidoglycan and mannosylated lipoarabinomannan partly recapitulated the subset partition induced by Mtb. Addition of IFN-gamma, but neither IL-17A nor IL-22, which are potentially produced by Mtb-exposed gamma/delta-T cells in mucosal linings, inhibited the differentiation toward CD14+ DCs and promoted high-level IL-12p70 in Mtb-challenged DCs. We conclude that Mtb exploits DC plasticity to reduce production of IL-12p70, and that this process is entirely divertible by exogenous IFN-gamma. These data suggest that strategies to increase local IFN-gamma production in the lungs of tuberculosis patients may boost host immunity toward Mtb.
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- Academic publications [238441]
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- Faculty of Medical Sciences [90373]
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