Suppressive effect of bacterial endotoxin on the expression of cell-mediated anti-Listeria immunity

Abstract

Intravenous injection of bacterial endotoxin into mice at any time during ongoing infection with Listeria monocytogenes resulted in a markedly increased multiplication of this organism in the liver and spleen. Experiments designed to investigate the basis of this infection-enhancing effect revealed that endotoxin was also capable of inhibiting the expression of adoptive T-cell-mediated anti-Listeria immunity if given to normal recipient mice up to 48 h before they were infused with protective T-cells. On the other hand, endotoxin had only a marginal effect on the expression of adoptive immunity if given to donor mice before their spleen cells were harvested for adoptive transfer. Taken together, these results indicate that endotoxin probably interferes with the antibacterial function of macrophages rather than with mediator lymphocytes. The additional finding that the infection-enhancing action of endotoxin could be greatly reduced by making mice "tolerant" to endotoxin suggests that the acquisition of tolerance to this effect of endotoxin may be an important adaptive mechanism in acquired resistance to infection with gram-negative bacteria.

Enhanced Phagocytosis and Bactericidal Activity of Hepatic Reticuloendothelial System During Endotoxin Tolerance

“…Livers were isolated from control and endotoxin-tolerant rats and perfused with a medium containing 5% homologous serum from either control or tolerant rats. After the addition of the E. coli (2 x 107 cells per ml) to the perfusate, the hepatic clearance of the bacteria was followed for 30 min. The highest activation of the hepatic reticuloendothelial system was observed when serum from tolerant animals was added to the perfusate.…”

“…It is generally accepted that circulating endotoxins (lipopolysaccharides, LPS) play an important role in the pathogenesis of infections with gram-negative bacteria (1,17,18) and that pretreatment with bacterial LPS can alter the host response to infection by modifying the mechanism of nonspecific resistance (8,30).…”

“…Phagocytosis and killing of E. coli by isolated rat liver perfused with serum-free perfusate,30 min after bacterial inoculum…”

Impaired function of immune reactivity to Listeria monocytogenes in diet-fed mice

“…Even at 14 and 21 days after infection, viable L. monocytogenes cells were present in livers of diet-fed animals (data not shown), a situation similar to that observed in nude mice (4). To establish whether sensitized spleen cells were being produced in these animals, an adoptive transfer of immunity experiment was performed, adapting previously described methods (5,9,11). * Corresponding author.…”

“…Animals to be used as spleen cell donors received either 103 CFU of L. monocytogenes or 108 sheep erythrocytes (specificity control) intravenously 6 days before spleen cell harvest. To reduce the number of contaminating L. monocytogenes cells in the spleen cell suspension, donors were inoculated subcutaneously with 10,000 U of penicillin G 24 h before spleen cell harvest, and 500 ,ug of ampicillin per ml was added to their drinking water (9). Spleen cell suspensions were prepared in RPMI 1640 medium by pressing the spleens through a stainless steel mesh, aspirating twice through a 21-gauge needle, and washing by centrifugation for 10 min at 300 x g. Cells were suspended in 25 ml of RPMI 1640 medium, and adherent cells were removed by incubation at 37°C for 1 h. Nonadherent cells were washed twice more by centrifugation, and a viable count was obtained using trypan blue.…”