Intracellular killing of Listeria monocytogenes by activated macrophages (Mackaness system) is due to antibiotic

Abstract

THE classic in vivo studies of Mackaness¹ showed that the macrophage could be activated to kill intracellular organisms such as Listeria monocytogenes. This led to a series of experiments to determine the process by studying killing of this organism by macrophages both in vivo and in vitro^2–6. Subsequent experiments carried out with Mackaness¹ system in vitro have required antibiotic or suitable serum in the culture medium to control extracellular growth of the organism which otherwise overruns the culture^7,8. Antibiotics have been shown to enter peritoneal cells⁹ and affect bacterial proliferation^10–12, although there is evidence that the intracellular environment to some extent protects bacteria against the effects of antibiotics^13,14. It has always been uncertain, therefore, whether any intracellular killing observed has been a result of antibiotic rather than activated cellular processes. Furthermore, antibiotic might be expected to enter activated cells more than resting ones, thereby causing an apparently increased intracellular killing by the former. Thus, in order to validate the system, it is necessary to prove that antibiotic is not involved in the killing of the organism. The crucial, but hitherto absent, control that is required must show true intracellular proliferation of the organism within activated cells in the face of antibiotic in the medium.