Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

S. Parlato, T. Chiacchio, D. Salerno, L. Petrone, L. Castiello, G. Romagnoli, I. Canini, D. Goletti, L. Gabriele

Research output: Contribution to journalArticle

Abstract

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. © 2018 Parlato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Original languageEnglish
JournalPLoS One
Volume13
Issue number1
DOIs
Publication statusPublished - 2018

    Fingerprint

Keywords

  • alpha interferon
  • antigen
  • leukocyte antigen
  • adult
  • Article
  • cell activation
  • cell differentiation
  • cell subpopulation
  • clinical article
  • comparative study
  • controlled study
  • dendritic cell
  • down regulation
  • female
  • gene
  • gene function
  • genetic transcription
  • human
  • human tissue
  • immune response
  • latent tuberculosis
  • male
  • monocyte
  • Mycobacterium tuberculosis
  • myeloid dendritic cell
  • phenotype
  • plasmacytoid dendritic cell
  • protein analysis
  • signal transduction
  • tuberculosis
  • immunology
  • middle aged
  • pathology
  • Adult
  • Antigens, CD
  • Dendritic Cells
  • Down-Regulation
  • Female
  • Humans
  • Interferon-alpha
  • Latent Tuberculosis
  • Male
  • Middle Aged

Cite this