ELIMINATION OF RESIDENT MACROPHAGES FROM THE LIVERS AND SPLEENS OF IMMUNE MICE IMPAIRS ACQUIRED-RESISTANCE AGAINST A SECONDARY LISTERIA-MONOCYTOGENES INFECTION

During a secondary Listeria monocytogenes infection in mice, the bacte ria are eliminated more rapidly from the liver and spleen than during a primary infection, This acquired resistance against a secondary infe ction is dependent on T lymphocytes, which induce enhanced elimination of bacteria via stimulation of effector cells such as neutrophils, re sident macrophages, exudate macrophages, and hepatocytes, The aim of t he present study was to determine the role of the resident macrophages in acquired resistance against a secondary L, monocytogenes infection in mice, Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose (LD(50)) oft. monocytogenes intravenously (i, v,), i,e,, immune mice, received a challenge of 1 LD(50) of L, monocyt ogenes i,v, to induce a secondary infection, At 2 days prior to challe nge, immune mice were given an i,v, injection of liposomes containing dichloromethylene-diphosphonate (L-Cl(2)MDP) to selectively eliminate resident macrophages from the liver and spleen, Control immune mice re ceived either phosphate-buffered saline (PBS) or liposomes containing PBS (L-PBS). Treatment of mice with L-Cl(2)MDP effectively eliminated resident macrophages from the liver and spleen but did not affect the number of granulocytes, monocytes, or lymphocytes in peripheral blood or their migration to a site of inflammation, Phagocytosis and killing of L, monocytogenes by peritoneal exudate cells elicited with heat ki lled L. monocytogenes were similar in all groups of immune mice, On da y 3 of a secondary infection, the number of L. monocytogenes organisms in the livers and spleens of L-Cl-2,MDP treated immune mice was 4 log (10) units higher than in immune mice treated with PBS or L-PBS. The c oncentration of reactive nitrogen intermediates in plasma, a measure o f the severity of infection, was 70-fold higher for L-Cl(2)MDP-treated immune mice than for PBS- or L-PBS-treated immune mice, Treatment wit h L-Cl(2)MDP significantly increased the number of inflammatory foci i n the liver and spleen, decreased their size, and affected their struc ture, From these results, we conclude that resident macrophages are re quired for the expression of acquired resistance against a secondary L , monocytogenes infection in mice.