title: NK cell activity in tuberculosis is associated with impaired CD11a and ICAM-1 expression: a regulatory role of monocytes in NK activation.
abstract: 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.
authors.affiliation: Immunology Department, Institute of Haemotology Research (IIHema), National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Schierloh
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alemán
authors.forename: Noemí
authors.initials: N
authors.lastname: Yokobori
authors.forename: Leandro
authors.initials: L
authors.lastname: Alves
authors.forename: Nicolás
authors.initials: N
authors.lastname: Roldán
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: María
authors.initials: M
authors.lastname: del C Sasiain
authors.forename: Silvia
authors.initials: S
authors.lastname: de la Barrera
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D040881:CD11a Antigen / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D040881:CD11a Antigen; D017252:CD3 Complex; D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D019409:Interleukin-15; D020382:Interleukin-18; D037181:Lectins, C-Type; D017452:Receptors, IgG; D000099192:CD69 Antigens