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

Abstract

We investigated the effect of glutaraldehyde-fixed Salmonella typhi Ty2 (Vi⁻) wild-type (World Health Organization’s vaccine strain) and mutant strains MEI028 (rough, O-antigen⁻) and MEI012 [smooth (O-antigen⁺) or rough (partially expressed O-antigen) phenotype when grown at 37 or 30°C, respectively] on natural killer (NK) cell activity of peripheral blood mononuclear cell (PBMC) samples and highly purified (HP; >95%), immunomagnetically isolated NK cell preparations. Incubation of PBMC with each and every one of the S. typhi strains studied consistently and significantly, increased this cellular immune function, as well as the supernatant level of the various cytokines tested e.g. IFN-γ, TNF-α, 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-γ and TNF-α) was detected in the supernatant.

Our results suggest that S. typhi O-antigen plays an essential role in a mechanism resulting in the direct activation of NK cell activity in HPNK cell preparations. However, the relative quantitative significance of this antigen in the direct stimulation of NK cell cytotoxicity expression in PBMC samples is less clear, as it appears that in this case bacterial-induced monocyte-released cytokines plays a most important role. Incubation with S. typhi Ty2 or MEI028 elicited significant expression of CD69, an early marker of NK cell activation, in PBMC but not in HPNK cell samples (flow cytometry); in similar experiments, the expression of CD16/56 and activation marker CD25 remained essentially unchanged.