Elimination of resident macrophages from the livers and spleens of mice impairs acquired resistance against a secondary Listeria monocytogenes infection

During a secondary Listeria monocytogenes infection in mice, the bacteria are eliminated more rapidly from the liver and spleen than during a primary infection. This acquired resistance against a secondary infection is dependent on T lymphocytes, which induce enhanced elimination of bacteria via stimulation of effector cells such as neutrophils, resident macrophages, exudate macrophages, and hepatocytes. The aim of the 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 (LD50) of L. monocytogenes intravenously (i.v.), i.e., immune mice, received a challenge of 1 LD50 of L. monocytogenes i.v. to induce a secondary infection. At 2 days prior to challenge, immune mice were given an i.v. injection of liposomes containing dichloromethylene-diphosphonate (L-Cl2MDP) to selectively eliminate resident macrophages from the liver and spleen. Control immune mice received either phosphate-buffered saline (PBS) or liposomes containing PBS (L-PBS). Treatment of mice with L-Cl2MDP 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. monocytogencs by peritoneal exudate cells elicited with heat-killed L. monocytogenes were similar in all groups of immune mice. On day 3 of a secondary infection, the number of L. monocytogenes organisms in the livers and spleens of L-Cl2MDP-treated immune mice was 4 log10 units higher than in immune mice treated with PBS or L-PBS. The concentration of reactive nitrogen intermediates in plasma, a measure of the severity of infection, was 70-fold higher for L-Cl2MDP-treated immune mice than for PBS- or L-PBS-treated immune mice. Treatment with L-Cl2MDP significantly increased the number of inflammatory foci in the liver and spleen, decreased their size, and affected their structure. From these results, we conclude that resident macrophages are required for the expression of acquired resistance against a secondary L. monocytogenes infection in mice.