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

Latent Tuberculosis
dendritic cells
tuberculosis
Dendritic Cells
Tuberculosis
Mycobacterium tuberculosis
Interferons
T-cells
Tissue Donors
interferons
infection
Immunity
T-Lymphocytes
Antigens
Mycobacterium Infections
Antigen Presentation
Conveying
Licensure
T-lymphocytes
immunity

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

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis. / Parlato, S.; Chiacchio, T.; Salerno, D.; Petrone, L.; Castiello, L.; Romagnoli, G.; Canini, I.; Goletti, D.; Gabriele, L.

In: PLoS One, Vol. 13, No. 1, 2018.

Research output: Contribution to journalArticle

@article{fa95f44cd46c4f759ee0fe753b2a04ef,
title = "Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis",
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. {\circledC} 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.",
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author = "S. Parlato and T. Chiacchio and D. Salerno and L. Petrone and L. Castiello and G. Romagnoli and I. Canini and D. Goletti and L. Gabriele",
note = "Cited By :1 Export Date: 11 April 2019 CODEN: POLNC Correspondence Address: Goletti, D.; Translational Research Unit, Department of Epidemiology and Preclinical Research, {"}L. Spallanzani{"}, National Institute for Infectious Diseases (INMI) IRCCSItaly; email: delia.goletti@inmi.it Chemicals/CAS: Antigens, CD; Interferon-alpha References: Lin, P.L., Flynn, J.L., CD8 T cells and Mycobacterium tuberculosis infection (2015) Semin Immunopathol, 37 (3), pp. 239-249. , https://doi.org/10.1007/s00281-015-0490-8, Epub 2015/04/29. PMID: 25917388; Petruccioli, E., Scriba, T.J., Petrone, L., Hatherill, M., Cirillo, D.M., Joosten, S.A., Correlates of tuberculosis risk: Predictive biomarkers for progression to active tuberculosis (2016) Eur Respir J, 48 (6), pp. 1751-1763. , https://doi.org/10.1183/13993003.01012-2016, Epub 2016/11/12. 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year = "2018",
doi = "10.1371/journal.pone.0189477",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

AU - Parlato, S.

AU - Chiacchio, T.

AU - Salerno, D.

AU - Petrone, L.

AU - Castiello, L.

AU - Romagnoli, G.

AU - Canini, I.

AU - Goletti, D.

AU - Gabriele, L.

N1 - Cited By :1 Export Date: 11 April 2019 CODEN: POLNC Correspondence Address: Goletti, D.; Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani", National Institute for Infectious Diseases (INMI) IRCCSItaly; email: delia.goletti@inmi.it Chemicals/CAS: Antigens, CD; Interferon-alpha References: Lin, P.L., Flynn, J.L., CD8 T cells and Mycobacterium tuberculosis infection (2015) Semin Immunopathol, 37 (3), pp. 239-249. , https://doi.org/10.1007/s00281-015-0490-8, Epub 2015/04/29. PMID: 25917388; Petruccioli, E., Scriba, T.J., Petrone, L., Hatherill, M., Cirillo, D.M., Joosten, S.A., Correlates of tuberculosis risk: Predictive biomarkers for progression to active tuberculosis (2016) Eur Respir J, 48 (6), pp. 1751-1763. , https://doi.org/10.1183/13993003.01012-2016, Epub 2016/11/12. 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PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - alpha interferon

KW - antigen

KW - leukocyte antigen

KW - adult

KW - Article

KW - cell activation

KW - cell differentiation

KW - cell subpopulation

KW - clinical article

KW - comparative study

KW - controlled study

KW - dendritic cell

KW - down regulation

KW - female

KW - gene

KW - gene function

KW - genetic transcription

KW - human

KW - human tissue

KW - immune response

KW - latent tuberculosis

KW - male

KW - monocyte

KW - Mycobacterium tuberculosis

KW - myeloid dendritic cell

KW - phenotype

KW - plasmacytoid dendritic cell

KW - protein analysis

KW - signal transduction

KW - tuberculosis

KW - immunology

KW - middle aged

KW - pathology

KW - Adult

KW - Antigens, CD

KW - Dendritic Cells

KW - Down-Regulation

KW - Female

KW - Humans

KW - Interferon-alpha

KW - Latent Tuberculosis

KW - Male

KW - Middle Aged

U2 - 10.1371/journal.pone.0189477

DO - 10.1371/journal.pone.0189477

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

ER -