Mechanisms of Acquired Resistance in Mouse Typhoid

Abstract

Experiments in vitro comparing normal mouse peritoneal macrophages with cells from Salmonella typhimurium-infected mice have shown that the "immune" macrophages have conspicuously enhanced microbicidal properties. Whereas normal macrophages could inactivate only 50 to 60% of intracellular S. typhimurium pretreated with immune serum, cells from infected animals killed virtually all ingested organisms and did so at an accelerated rate. Macrophages from Listeria monocytogenes-infected mice were shown to possess similarly enhanced microbicidal activity against S. typhimurium. Furthermore, the growth of S. typhimurium in the liver and spleen was more effectively restricted in Listeria-infected mice than in animals vaccinated with heat-killed S. typhimurium, even though the Listeria-infected animals possessed no demonstrable cross-reacting antibody to S. typhimurium. The lack of resistance in the mice vaccinated with heat-killed organisms could not be attributed to any deficiency of humoral factors, since the serum from these animals was as effective at promoting phagocytosis and killing by macrophages as serum from actively infected (and demonstrably resistant) mice. Conversely, Salmonella-infected mice were totally resistant to intravenous challenge with L. monocytogenes. The level of resistance in individual animals was related to the numbers of residual Salmonellae remaining in the tissues; mice with heavier residual infections being the more resistant. Specific antiserum from mice vaccinated with heat-killed S. typhimurium was found to be significantly protective only when the intraperitoneal route of challenge was employed. The foregoing studies have been interpreted to mean that enhancement of the microbicidal ability of macrophages is the mechanism of major importance in acquired resistance to S. typhimurium infection in mice.

Mechanism of the Protective Action of Anti-Salmonella IgM in Experimental Mouse Salmonellosis

“…The effect of antibodies in mouse salmonellosis is restricted in several ways: (i) it is clearcut against IP but negligible against IV challenge Jenkin & Rowley, 1963;Blanden et al, 1966); (ii) it is almost exclusively mediated by the IgM class of anti-Salmonella antibodies (Saxkn & Miikelii, 1982;Saxkn et al, 1984b); and (iii) as shown in the present study, their effect is restricted to the very early phase of the infection. The data presented here help to explain each of these restrictions by showing where in the infectious process the antibodies intervene.…”

“…Both cellular and humoral immunity play a role in the defence but their relative contributions are still under debate (Levine & Hornick, 1981). The route of infection influences the course of the infection, but we do not know, for example, why intraperitoneally (IP) induced infection is more easily prevented by antibodies than is infection after intravenous (IV) challenge Jenkin & Rowley, 1963;Blanden et al, 1966).…”

Division and Death Rates of Salmonella typhimurium Inside Macrophages: Use of Penicillin as a Probe

“…I N T R 0 D U C T I 0 N Whether salmonellae increase or decline in number within macrophages after phagocytosis, a factor crucial to the outcome of infection with these facultative intracellular parasites (Jenkin & Rowley, 1963;Blanden et al, 1966), depends on the balance between bacterial division and death rates in the intracellular environment. Studies with macrophages in vitro show that virulent salmonellae are more capable than avirulent organisms of increasing intracellularly (Furness, 1958 ;Furness & Ferreira, 1959 ;Jenkin & Benacerraf, 1960) and that macrophages from immune animals are better able to restrict intracellular proliferation than those from susceptible animals (Jenkin & Benacerraf, 1960;Blanden, 1968;Maier & Oels, 1972).…”

Cellular Mechanisms in the Protection against Infection by Listeria monocytogenes in Mice

“…Furthermore, macrophages activated by listeria infection also inhibit intracellular growth of Salmonella typhimurium (Blanden, Mackaness & Collins, 1966) and Candida albicans (Marra & Balish, 1974). Thymus-derived (T) lymphocytes are required for activation of macrophages both in vivo and in vitro (Lane & Unanue, 1972;North, 1g73a;Cole, 1975).…”