Human primary dendritic cells (DCs) are heterogeneous by phenotype, function,
and tissue localization and distinct from inflammatory monocyte-derived DCs.
Current information regarding the susceptibility and functional role of
primary human DC subsets to Mycobacterium tuberculosis (Mtb) infection is
limited. Here, we dissect the response of different primary DC subsets to Mtb
infection. Myeloid CD11c+ cells and pDCs (C-type lectin 4C+ cells) were
located in human lymph nodes (LNs) of tuberculosis (TB) patients by
histochemistry. Rare CD141hi DCs (C-type lectin 9A+ cells) were also
identified. Infection with live Mtb revealed a higher responsiveness of
myeloid CD1c+ DCs compared to CD141hi DCs and pDCs. CD1c+ DCs produced
interleukin (IL)-6, tumor necrosis factor α, and IL-1β but not IL-12p70, a
cytokine important for Th1 activation and host defenses against Mtb. Yet,
CD1c+ DCs were able to activate autologous naïve CD4+ T cells. By combining
cell purification with fluorescence-activated cell sorting and gene expression
profiling on rare cell populations, we detected in responding CD4+ T cells,
genes related to effector-cytolytic functions and transcription factors
associated with Th1, Th17, and Treg polarization, suggesting multifunctional
properties in our experimental conditions. Finally, immunohistologic analyses
revealed contact between CD11c+ cells and pDCs in LNs of TB patients and in
vitro data suggest that cooperation between Mtb-infected CD1c+ DCs and pDCs
favors stimulation of CD4+ T cells