Samsom J N, Annema A, Groeneveld P H, van Rooijen N, Langermans J A, van Furth R
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Infect Immun. 1997 Mar;65(3):986-93. doi: 10.1128/IAI.65.3.986-993.1997.
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. monocytogenes 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.
在小鼠的单核细胞增生李斯特菌二次感染过程中，与初次感染相比，细菌从肝脏和脾脏中清除得更快。这种对二次感染的获得性抗性依赖于T淋巴细胞，T淋巴细胞通过刺激效应细胞（如中性粒细胞、驻留巨噬细胞、渗出液巨噬细胞和肝细胞）来增强细菌的清除。本研究的目的是确定驻留巨噬细胞在小鼠对单核细胞增生李斯特菌二次感染的获得性抗性中的作用。从静脉注射0.1 50%致死剂量（LD50）的单核细胞增生李斯特菌的亚致死初次感染中恢复的小鼠，即免疫小鼠，静脉注射1 LD50的单核细胞增生李斯特菌以诱导二次感染。在攻击前2天，给免疫小鼠静脉注射含有二氯亚甲基二膦酸盐（L-Cl2MDP）的脂质体，以选择性地清除肝脏和脾脏中的驻留巨噬细胞。对照免疫小鼠接受磷酸盐缓冲盐水（PBS）或含有PBS的脂质体（L-PBS）。用L-Cl2MDP处理小鼠有效地清除了肝脏和脾脏中的驻留巨噬细胞，但不影响外周血中粒细胞、单核细胞或淋巴细胞的数量或它们向炎症部位的迁移。在所有免疫小鼠组中，用热灭活的单核细胞增生李斯特菌引发的腹膜渗出细胞对单核细胞增生李斯特菌的吞噬和杀伤作用相似。在二次感染的第3天，用L-Cl2MDP处理的免疫小鼠肝脏和脾脏中的单核细胞增生李斯特菌数量比用PBS或L-PBS处理的免疫小鼠高4个对数10单位。血浆中反应性氮中间体的浓度是感染严重程度的一个指标，用L-Cl2MDP处理的免疫小鼠比用PBS或L-PBS处理的免疫小鼠高70倍。用L-Cl2MDP处理显著增加了肝脏和脾脏中炎症灶的数量，减小了它们的大小，并影响了它们的结构。从这些结果中，我们得出结论，驻留巨噬细胞是小鼠对单核细胞增生李斯特菌二次感染获得性抗性表达所必需的。
