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

Abstract

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.

Insights on the crosstalk between dendritic cells and helper T cells in novel genetic etiology for mendelian susceptible mycobacterial disease

“…Further, when SPPL2 inhibitors were added to those cord bloodderived DCs accumulation of CD74 was observed in the cDC2 population. 2 Consistently with this notion, the frequency of pDCs and cDC2 was reduced in untreated Tuberculosis patients 16 and impaired frequency and functionality of DCs has been previously reported for MSMD patients with a IRF-8 deficiency. 12 Importantly, Kong et al also evaluated whether the SPPL2a deficiency affected IL12p40 production, due to the low frequency of the cDC2 population, however, no significant differences were observed as compared to healthy controls.…”

Identification of Mycobacterium tuberculosis Infection in Infants and Children With Partial Discrimination Between Active Disease and Asymptomatic Infection

“…As the proportions of blood monocytes and DC subsets were reported to be altered during M. tuberculosis infection in adults (23), we conducted a pilot study for 25/130 children to characterize these parameters, as this can be done by flow cytometry on a small blood volume. In contrast to adults, the proportions of the three different subsets of monocytes identified by their CD14 and CD16 expression were not different between NI children and infected children (LTBI or aTB) (Supplementary Table).…”

“…When the blood volume was sufficient (for 25 children—Supplementary Table), 100 μl of additional undiluted blood was stained ex-vivo with different monoclonal antibodies in order to identify monocyte and DC subsets as described (23). Briefly, fresh whole blood was stained for 30 min at room temperature in the dark with monoclonal antibodies to the following surface markers: CD3-FITC, CD19-FITC, CD56-FITC, CD141-PE, CD123-PerCpCy5.5, HLA-DR-PE-Cy7, CD16-APC, CD45-APC-H7, CD11c-V450, and CD14-V500 (all from BD Biosciences, except anti-CD141 from Miltenyi and anti-CD45 from Biolegend).…”

“…The median number of acquired CD45 + cells was 172,000 (25th−75th percentiles = 144,000–208,000). A sequential gating strategy was applied as described (23), allowing us to identify the three subsets of monocytes (CD14 + CD16 − , CD14 + CD16 + , CD14 − CD16 + ) and of DCs (CD123 + CD11c − plasmacytoid DC (pDC), CD123 − CD11c + CD141 − type 1 myeloid DC (mDC) or CD123 − CD11C + CD141 + type 2 mDC). The results of the different monocyte subsets and of the pDC and mDC subsets are expressed as percentages among CD45 + cells.…”

“…The second aim was to evaluate whether, in contrast to the TST, these tests could help the clinician to differentiate, at least partially, children with LTBI from those with aTB among M. tuberculosis- infected children. Finally, the third aim was to evaluate in a pilot study, the potential added value for this differentiation between LTBI and aTB of the blood monocyte and dendritic cell (DC) subsets characterization by flow cytometry, based on our recent publication in adults (23).…”