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J Leukoc Biol. 2018 May;103(5):945-954. doi: 10.1002/JLB.4A1117-448R. Epub 2018 Feb 28.

Blood tolerogenic monocytes and low proportions of dendritic cell subpopulations are hallmarks of human tuberculosis.

Author information

1
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
2
Department of Internal Medicine and Infectious Diseases, UZ Brussel, Brussels, Belgium.
3
Department of Internal Medicine and Infectious Diseases, Hôpital Erasme, Brussels, Belgium.
4
Laboratory of Molecular Immunodiagnostics, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
5
Immunobiology Clinic, Hôpital Erasme, Brussels, Belgium.

Abstract

BACKGROUND:

The immune mechanisms underlying the pathogenesis of tuberculosis (TB) need better understanding to improve TB management, as the disease still causes more than 1.5 million deaths annually. This study tested the hypothesis that a modulation of the proportions or activation status of APC during Mycobacterium tuberculosis infection may impact on the course of the disease.

PROCEDURE:

Proportions of circulating APC subsets and the expression of stimulatory (CD86), inhibitory (ILT-3, ILT-4, ILT-7), or apoptosis-inducing (PDL-1, PDL-2) molecules were analyzed in 2 independent cohorts, on blood monocytes and dendritic cell (DC) subsets from patients with active or latent TB infection (aTB /LTBI) and from uninfected subjects.

RESULTS:

Higher proportions of classical CD14+ CD16- and intermediate CD14+ CD16+ monocytes, and lower proportions of plasmacytoid DC (pDC) and type 2 myeloid DC were observed in the blood from untreated patients with aTB compared with those with LTBI and with healthy subjects, with an early normalization of the proportions of pDC during treatment. In addition, monocytes from M. tuberculosis-infected subjects expressed higher levels of ILT-3, ILT-4, and PDL-1 compared with healthy controls, these differences being more important for patients with aTB than for those with LTBI.

CONCLUSIONS:

These results confirm the hypothesis of a modulation of the proportions and activation status of APC during M. tuberculosis infection and suggest that these cells could play a role in driving the course of M. tuberculosis infection.

KEYWORDS:

ILT-3+ monocytes; PDL-1+ monocytes; myeloid type 2 dendritic cells; plasmacytoid dendritic cells

PMID:
29489031
DOI:
10.1002/JLB.4A1117-448R
[Indexed for MEDLINE]

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