Effect of Salmonella typhi wild type and O-antigen mutants on human natural killer cell activity

We investigated the effect of glutaraldehyde-fixed Salmonella typhi Ty2 (Vi (-)) wild-type (World Health Organization's vaccine strain) and mutant stra ins MEI028 (rough, O-antigen(-)) and ME1012 [smooth (O-antigen(+)) or rough (partially expressed O-antigen) phenotype when grown at 37 or 30 degrees C , respectively] on natural killer (NK) cell activity of peripheral blood mo nonuclear cell (PBMC) samples and highly purified (HP; >95%), immunomagneti cally isolated NK cell preparations. Incubation of PBMC with each and every one of the S. typhi strains studied consistently and significantly, increa sed this cellular immune function, as well as the supernatant level of the various cytokines tested e.g. IFN-gamma, TNF-alpha, IL-10 and IL-12 (ELISA) . In similar experiments, a significant increase in the cytolytic activity of HPNK cells was elicited by S. typhi Ty2 but not by mutant strain MEI028; neither of the cytokines assayed (IFN-gamma and TNF-alpha) was detected in the supernatant. Our results suggest that S, typhi O-antigen plays an essential role in a me chanism resulting in the direct activation of NK cell activity in HPNK cell preparations. However, the relative quantitative significance of this anti gen in the direct stimulation of NK cell cytotoxicity expression in PBMC sa mples is less clear, as it appears that in this case bacterial-induced mono cyte-released cytokines plays a most important role. Incubation with S. typ hi Ty2 or MEI028 elicited significant expression of CD69, an early marker o f NK cell activation, in PBMC but not in HPNK cell samples (flow cytometry) ; in similar experiments, the expression of CD16/56 and activation marker C D25 remained essentially unchanged. (C) 2000 International Society for Immu nopharmacology. Published by Elsevier Science Ltd. All rights reserved.