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

作者：Dirix Violette; Corbiere Veronique; Wyndham Thomas Chloe; Selis Elodie; Allard Sabine; Hites Maya; Aerts Laetitia; Giese Thomas; Mascart Francoise^*

来源：Journal of Leukocyte Biology, 2018, 103(5): 945-954.

DOI：10.1002/JLB.4A1117-448R

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

BackgroundThe 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.
ProcedureProportions 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.
ResultsHigher 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.
ConclusionsThese 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.
Altered proportions and phenotype of blood monocyte and dendritic cells subpopulations are biomarkers for active tuberculosis in humans and may have a role in pathogenesis.

• 出版日期2018-5