A subset of CD1c+ dendritic cells is increased in patients with tuberculosis and promotes Th17 cell polarization

Abstract

The role of primary subsets of DCs in Mycobacterium tuberculosis infection in humans is incompletely understood. In this study, we identified a CD1c DC subset with phenotype of CD1c+CD11c+CD19−CD11b+ that was significantly increased in tuberculous pleural effusions and in peripheral blood from patients with TB compared with that from healthy controls (p < 0.0001). Sputum smear/culture-positive patients with tuberculosis had significantly higher frequency of CD1c+CD11b+ DC subset than sputum smear/culture-negative patients (p < 0.0001). After effective anti-TB chemotherapy, the frequency of CD1c+CD11b+ DC subset in peripheral blood and tuberculous pleural effusions was decreased. CD1c+CD11b+ DC subset from tuberculous pleural effusions expressed higher levels of TLR2, TLR4, CD172a, CD206 and FcεRⅠ, but lower levels of CD80, CD83 and CD86 compared with CD1c+CD11b− DC subset. Expression of IL-1β, IL-6, IL-8, IL-23, TNF-α, IFN-γ and TGF-β mRNA in CD1c+CD11b+ DCs was higher than in CD1c+CD11b− DC subset. Co-culture of autologous naive CD4+ T cells with sorted CD1c+CD11b+ DCs expressed significantly increased levels of IL-17A and RORγt transcripts as compared with those co-cultured with CD11b− subset. In conclusion, a CD1c+CD11b+ DC subset with elevated frequency in patients with tuberculosis was identified and it promoted Th17 cell differentiation.