title: Communication between Human Dendritic Cell Subsets in Tuberculosis: Requirements for Naive CD4(+) T Cell Stimulation.
abstract: 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 CD141(hi) DCs (C-type lectin 9A(+) cells) were also identified. Infection with live Mtb revealed a higher responsiveness of myeloid CD1c(+) DCs compared to CD141(hi) 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.
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Laura
authors: L
authors: Lozza
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Maura
authors: M
authors: Farinacci
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Marina
authors: M
authors: Bechtle
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Manuela
authors: M
authors: Stäber
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Ulrike
authors: U
authors: Zedler
authors: Pathology Division, National Institute for Infectious Disease 'Lazzaro Spallanzani' , Rome , Italy.
authors: Andrea
authors: A
authors: Baiocchini
authors: Pathology Division, National Institute for Infectious Disease 'Lazzaro Spallanzani' , Rome , Italy.
authors: Franca
authors: F
authors: Del Nonno
authors: Department of Immunology, Max Planck Institute for Infection Biology , Berlin , Germany.
authors: Stefan H E
authors: SH
authors: Kaufmann
keywords: CD141hi DCs; CD1c+ DCs; CD4+ T cells; Mycobacterium tuberculosis; human; plasmacytoid DCs