Differential expression of maturation and activation markers on NK cells in patients with active and latent tuberculosis

NK cells were recently suggested to be important for the initial control of M. tuberculosis infection. The phenotypes of the 3 main NK blood subsets, CD56(bright), CD56(dim), and CD56(neg) cells, were characterized by flow cytometry in a cohort of 81 prospectively enrolled subjects (21 untreated patients with active tuberculosis -aTB-, 35 latently TB infected -LTBI- subjects, and 25 non-infected controls), using 9 different mAbs added to whole blood. Compared to LTBI subjects, patients with aTB had lower proportions of total NK cells, lower proportions and numbers of CD56(neg) cells expressing early maturation markers (CD161, NKp30, NKp46), but higher density of NKp30 and NKp46 expression on both CD56(neg) and CD56(dim) subsets, associated with higher expression of granzymes A/B. They also had higher proportions of activated CD69(pos) cells within all 3 NK cell subsets and, the percentage of CD69(pos) CD56(dim) cells among CD69(pos) and/or NKG2C(pos) NK cells was identified as a potential biomarker to discriminate aTB from LTBI. LTBI subjects were in contrast characterized by higher expression of late maturation markers (CD57, KIR molecules) on the CD56(neg) subset, by higher proportions of NKG2C(pos)KIR(pos) CD56(dim) NK cells, and by higher in vitro IFN-gamma production than patients with aTB. Thus, the in-depth phenotypic characterization of blood NK cell subsets provides new insights on possible functional modifications and the potential role of NK cells in the control of M. tuberculosis infection in humans.