NK cell activity in tuberculosis is associated with impaired CD11a and ICAM-1 expression: a regulatory role of monocytes in NK activation.

Although the role of natural killer (NK) cells in mycobacterial infections is unclear, it has been postulated that they contribute to protective immunity through the production of interferon (IFN)-gamma. In this study, we evaluate the effect of interleukin (IL)-10, IL-15 and IL-18 on NK lytic activity through the expression of CD16, CD11a and CD69 molecules and the induction of IFN-gamma production in patients with tuberculosis (TB) and healthy individuals (N). Our results showed an impairment of NK lytic activity and a gradual down-regulation of costimulatory and adhesion molecules on NK cells which were dependent on the severity of the disease. NK lytic activity was increased by exogenous IL-15 and IL-18 in both TB and N, and by neutralization of endogenous IL-10 only in TB; IL-15 and IL-18 increased CD69 receptor expression, while anti-IL-10 up-regulated CD16 and CD11a expression in TB. Mycobacterium tuberculosis reduced the number of intracellular adhesion molecule (ICAM)-1(+) CD14(+) cells, but in the presence of IL-15, IL-18 and anti-IL-10 its expression was up-regulated. In cells from TB patients, the observed effects of IL-15 and IL-18 on NK function were not dependent on IL-10 modulation of the surface expression of activator/adhesion molecules. In the absence of monocytes, IL-10 activated NK cells, suggesting an indirect effect on their function. Furthermore, in TB patients the depletion of monocytes increased the production of IFN-gamma by NK cells. Therefore, monocytes from TB patients regulated the NK function involving IL-10 which, through an indirect mechanism, led to the down-regulation of costimulatory/adhesion molecules and/or IFN-gamma production.