S. Typhi Vaccine Strain Ty21a Can Cause a Generalized Infection in Whole Body-Irradiated But Not in Hydrocortisone-Treated Mice

Various mutations including galE- in the S.typhi vaccine strain Ty21a are thought to prevent proliferation of these micro-organisms in the host, and elimination of Ty21a would occur independent of the immune system of the host. To investigate this issue, we determined whether Ty21a can proliferate in immunosuppressed mice, and assessed the role of phagocytes in the eradication of Ty21a from tissues. Mice were rendered lymphocytopenic and monocytopenic by hydrocortisone s.c., or were made leucocytopenic by whole body irradiation. Bacteria were injected into a tail vene to evaluate eradication from the blood, liver and spleen, and into thigh muscle, i.e. a tissue that lacks resident macrophages. Ty21a were grown overnight in glucose [glu], or galactose and glucose [gal.glu]; only the Ty21a [gal.glu] expressed somatic O-antigens. After i.v. injection of 10(4) to 10(6) micro-organisms, Ty21a were rapidly eliminated from the liver and spleen of normal and immunosuppressed mice, i.e. within 1 day a 95% reduction of bacterial counts was observed. After i.m. injection of 10(4) to 10(6) bacteria, the number of viable Ty21a decreased in normal and hydrocortisone-treated mice, but in irradiated mice the micro-organisms proliferated and caused generalized infection. In all cases, Ty21a [glu] was eliminated more rapidly than Ty21a [gal.glu], confirming reports that killing of bacteria that lack O-antigens is more rapid than that of smooth bacteria of the same species. These results indicate that elimination of the vaccine strain against typhoid fever, Ty21a, from host tissues is not due to an intrinsic property of the micro-organisms that prevents proliferation but instead depends on the action of resident macrophages and exudate monocytes and granulocytes.