Effect of iron on antibacterial immunity in vaccinated mice

Abstract

The effect of iron on resistance to Salmonella typhimurium was investigated in mice inoculated with vaccines prepared from live and avirulent (SL3770) or killed and virulent (SR11 or LT2) bacteria. It has been found that mice vaccinated with SL3770 vaccine develop an immunity which can be neutralized with iron. Iron promoted the development of lethal infections by serving as a growth-essential nutrilite for infecting bacteria and by neutralizing the acquired immunity. The titration of this dual effect of iron showed that more iron was needed to neutralize the immunity in vaccinated animals than to promote bacterial growth in normal animals. In the presence of a sufficient amount of exogenous iron, as few as 10 bacteria caused lethal infections in normal and immune mice with the same effectiveness. This iron-sensitive immunity could be changed to iron-resistant immunity by the immunological stimulation of SL3770-vaccinated mice with a sonicated vaccine prepared from heat-killed SR11 or LT2 bacteria. In distinction to iron-sensitive immunity, iron-resistant immunity could be transferred from SR11or LT2-stimulated to normal mice with serum. Although effective in the transfer of antibacterial immunity, sera of SR11or LT2-stimulated mice supported the growth of virulent bacteria as well as did sera of normal mice. The absorption of immune serum with either SR11 or LT2 bacteria removed its protective quality, but the sensitized bacteria remained as infectious as untreated bacteria for iron-treated normal mice. Only in SL3770-vaccinated mice were the immune serum-sensitized bacteria not able to cause the infection in spite of daily treatment with iron. These results suggest that iron-resistant immunity is due to the synergistic action of specific antibody and phagocytes of immunologically stimulated animals.

The ability of Salmonella typhimurium to produce the siderophore enterobactin is not a virulence factor in mouse typhoid

“…When serum iron levels are elevated either experimentally or due to hemolytic disease the severity of bacterial infections, including those caused by S. typhimurium, is universally increased (1,3,7,10,25,32,44). We feel that this large body of data does indicate an effect of iron levels on pathogenesis, but that, at least in the case of S. typhimurium, the different serum iron levels probably exert their effect either by modulating the immune system (18,23) or by changing the levels of iron intracellularly, where siderophores are not required for its acquisition.…”