In Vitro Studies on T H E Interaction between Mouse Peritoneal Macrophages and Strains of Salmonella and Escherichia Coli* by Charles Jenkin,$ Ph.d., and Baruj Benacerraf, M.d

Studies on Salmonella infections in mice showed that the injected bacteria are cleared rapidly from the circulation, and may be found mainly in the liver, and spleen, the principal organs of the reticuloendothelial system (RES) (1). Investigations of the fate of the bacteria in these organs revealed that whereas the population of a virulent strain of Salmonella increases, that of an avirulent strain slowly declines (2, 3). Since mouse serum appears to lack a bactericidal mechanism in vitro, it has been assumed that the destruction of bacteria by the mouse is dependent on its cellular defenses (4, 5). Thus it has been suggested that the virulence of strains of Salmonella for the mouse reflects the ability of the strain to multiply within the phagocytic cells, presumably those of the RES. The technical difficulties involved in a study of the fate of Salmonella strains, within the fixed phagocytic ceils of the liver and spleen, has led workers to investigate the behaviour of bacteria of known virulence within peritoneal macrophages, or other animal ceils easily maintained in tissue culture (6--8). The results of these experiments in different laboratories have been contradictory. Furness (6) found that mouse peritoneal macrophages phagocytosed virulent and avirulent strains of Salmonella to the same extent in the presence of 10 per cent heated calf serum. After an initial period of killing, the virulent strain multiplied within the mononuclear ceils, whilst the avirulent strain maintained itself only in small numbers. These results are contrary to the findings of Rowley and Whitby (7) who studied the fate of the same strains of Salmonella typhimurium within mouse macrophages. These workers observed that the virulent strain required a greater amount of serum opsonins for phagocytosis than the avirulent strains, but once within the phagocyte both strains were killed at the