Effect of salmonella-infected human monocytes on natural killer cell cytotoxicity. In vitro studies

Various chemicals, including some bacteria-derived components, modulate nat ural killer cell (NKC) activity. We have analyzed the effect of wild-type T y2 and of mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 c ells and human autologous monocytes) on NKC cytotoxicity of peripheral bloo d mononuclear cell (PBMC) and highly purified NKC (HPNKC: CD16(+)/56(+) > 9 5%: the rest corresponding to CD3(+) T-cells). PBMC's co-culture with either S. typhi strain infected U937 cells (medium o r non-infected U937 cells as controls) resulted in the induction of lymphoc yte activated killer (LAK) cell activity showing cytotoxicity against targe t human NKC-resistant lymphoblastoid Daudi cell line. Comparable experiment s using autologous monocytes gave similar results. Co-culture of HPNKC prep arations with either S. typhi strain infected U937 cells resulted in increa sed LAK cell activity against target Daudi cells in each and everyone of th e five samples tested, paired Student's t-test p < 0.01 for both times (20 and 40 h) tested. Similar to the results observed in the experiments using PBMC, we did not find significant differences in the ability between medium and non-infected cells, or between wild-type S. typhi Ty2 and mutant strai n TYT1231 infected U937 cells, to induce LAK activity in HPNKC preparations . PBMC co-incubation with either S. typhi strain infected U937 cells or autol ogous monocytes resulted in significant increases in IL-12, TNF-alpha, and IFN-gamma secretion. In similar experiments using HPNKC samples instead, in fected U937 cells significantly increased IL-12 and IFN-gamma, but not TNF- alpha secretion. PBMC co-incubation with non-infected U937 cells, but not w ith non-infected monocytes, significantly increased supernatant IL-12 and T NF-alpha levels (no significant changes in IFN-gamma were recorded). Secret ed cytokines remained essentially unchanged after co-incubating HPNKC prepa ration with non-infected U-937 cells. Incubation of PBMC or HPNKC preparations with tither S. typhi strain infect ed U-937 cells failed to produce significant changes in the expression of N KC lineage (CD16(+)/56(+)) or activation (CD28(+), CD69(+) and CD95(+)) mar kers. The ability of infected monocytes to induce LAK activity, release NKC cytokines and upmodulate NKCs CD95(+) marker expression was essentially th e same for both infecting Salmonella strains used. These results suggest a role for NKC physiological defensive response against intracellularly infec ted monocytes representing, perhaps one of the antimicrobial mechanisms of the innate immune system. (C) 2001 Elsevier Science B.V. All rights reserve d.