SALMONELLA-TYPHI VACCINE STRAIN TY2LA 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 Ty21 a 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 T y21a can proliferate in immunosuppressed mice, and assessed the role o f phagocytes in the eradication of Ty21a from tissues. Mice were rende red 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 spl een, and into thigh muscle, i.e. a tissue that lacks resident macropha ges. Ty21a were grown overnight in glucose [glu], or galactose and glu cose [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 ra pidly eliminated from the liver and spleen of normal and immunosuppres sed mice, i.e. within 1 day a 95% reduction of bacterial counts was ob served. 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 microorganisms proliferated and caused general ized 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 sam e species. These results indicate that elimination of the vaccin strai n against typhoid fever, Ty21a, from host tissues is not due to an int rinsic property of the micro-organisms that prevents proliferation but instead depends on the action of resident macrophages and exudate mon ocytes and granulocytes.