Effect of free or liposome-encapsulated muramyl dipeptide on uptake and intracellular survival of Listeria monocytogenes in mouse peritoneal macrophages in vitro.

The effect of free versus liposome-encapsulated muramyl dipeptide (MDP) on the uptake and intracellular survival of Listeria monocytogenes in mouse peritoneal macrophages in vitro was investigated. Macrophages in monolayer culture were exposed to free MDP at various concentrations during different time periods before incubation with Listeria monocytogenes. An increase in bacterial uptake dependent on the concentration of MDP and the length of exposure was observed. Exposure of macrophages to 200 micrograms of free MDP per milliliter for 15 h led to a threefold increase in bacterial uptake, resulting in an average of 15 bacteria per macrophage after 30 min of incubation. In addition, intracellular bacteria were killed in the MDP-exposed macrophages, in contrast to the intracellular multiplication of Listeria monocytogenes in macrophages not exposed to MDP. Encapsulation of MDP within liposomes resulted in a significant enhancement of its activity: liposomal encapsulation led to a 1,000-fold reduction in the amount of MDP required to obtain these effects on bacterial uptake and intracellular killing, whereas empty liposomes had no effect at all. Liposomal encapsulation may be an appropriate means of increasing delivery of the muramyl peptides to the macrophages.