Natural Killer Cell Subpopulations in Putative Resistant Individuals and Patients with Active Mycobacterium tuberculosis Infection

Abstract

Herein, we intended to perform flow‐cytometric analyses of peripheral blood NK‐cell subsets in patients with active tuberculosis (TB) and those putative resistant subjects displaying positive tuberculin skin test (TST+) and compared with TST− healthy controls. Our findings demonstrated distinct phenotypic features in TST+ as compared with TB. While lower values of NK‐cells with increased frequency of CD3−CD16+ CD56− and CD3−CD16−CD56+ subsets besides lower frequency of CD3−CD16+ CD56+ NK‐cells was observed in TST+, unaltered levels of NK‐cells with increased levels of CD3−CD16+ CD56− NK‐cells with lower frequency of CD3−CD16+ CD56+ NK‐cells was found in TB. Additional analysis highlighted a shift towards increased levels of CD3−CD16−/+CD56bright NK‐cells as the hallmark of TST+, whereas unaltered frequency was observed in TB. Increased levels of CD3+CD56+ cells were observed in both TST+ and TB. Further focusing on the monocyte/NK‐cell network, we have reported that enhanced frequency of CD14+ CD16+ monocytes particularly observed in TST+. Outstanding were the distinct correlation profiles observed between CD3−CD16−CD56+ NK‐cells and CD3+ CD56+ cells CD14+ CD16+ monocytes for TST+ and TB. These data suggested that high levels of CD3−CD16−CD56+ NK‐cells aside CD14+ CD16+ monocytes as well as non‐concurrent increment of CD3+ CD56+ cells, may be involved in protective mechanisms in putative tuberculosis‐resistant individuals. On the other hand, the basal levels of macrophage‐like monocytes despite its positive correlation with increased levels of CD3+ CD56+ cells may count for the lack of the protective immunity in patients with active tuberculosis. Further studies focusing on the cytokine profiling of peripheral blood innate immunity cells before and after chemotherapic treatment are currently under evaluation.

Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development

“…Increased percentage of CD56 bright NK cells with normal numbers of total NK cells have been observed in different physiological and pathological conditions [20]–[24], but none of them seem to be plausible in the patient herein studied. Recently, two reports described mutations in the minichromosome maintenance complex component 4 (MCM4) that caused NK cell deficiency and adrenal insufficiency [25], [26].…”

CD56bright natural killer (NK) cells: an important NK cell subset

“…Exactly the same picture, i.e. reduction of NK cell numbers but increased percentage of CD56 bright NK cells, was found among individuals with a positive tuberculin skin test (TST + ) compared with patients with overt tuberculosis and normal controls 42 …”

Natural killer cells are recruited during pulmonary tuberculosis and theirex vivoresponses to mycobacteria vary between healthy human donors in association withKIRhaplotype

“…In humans, several clinical studies have explored the potential association between peripheral blood NK cell counts and resistance or susceptibility to tuberculosis (Barcelos et al ., 2008; Bozzano et al ., 2009; Leung et al ., 2009). A reduction in frequency and functionality of CD56 bright NK cells has been observed in patients with active tuberculosis and reciprocally, high blood levels were associated with protection in putative tuberculosis-resistant individuals.…”