Langermans J A, van der Hulst M E, Nibbering P H, van Furth R
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
J Immunol. 1990 Jun 1;144(11):4340-6.
Our study was performed to investigate whether macrophages become activated during an infection with Salmonella typhimurium and, if so, whether these activated macrophages kill S. typhimurium faster than resident macrophages. Mice received i.v. injections with a sublethal number of S. typhimurium; on about day 12 of the infection the numbers of bacteria in the liver and the spleen were maximal. During the infection, activation of peritoneal macrophages could be demonstrated on the basis of three criteria, i.e., the ability to inhibit the proliferation of Toxoplasma gondii, an enhanced production of H2O2 and an increased expression of Ia Ag. The rate of in vitro intracellular killing of S. typhimurium by these activated macrophages was not increased compared to that for resident macrophages. To determine the growth of S. typhimurium in activated mice a nalidixic acid-resistant mutant strain, called S. typhimurium 510R, was used. The net growth rates of the mutant S. typhimurium 510R in the spleen of S. typhimurium 510-activated and normal mice were similar. However, in the liver of S. typhimurium 510-activated mice the number of S. typhimurium 510R did not change during 3 to 48 h after injection. The role of specific antibodies during the initial phase of the infection was negligible, because only low levels of antibodies were detected during the first 15 days of infection and the growth rates of S. typhimurium 510 in the spleen and liver of mice with high titers of antibodies were not significantly different from the rates in normal mice. The results of this study demonstrate that although macrophages become activated during an infection with S. typhimurium, these cells do not display an enhanced bactericidal activity in vitro and in vivo no significant effect on the growth rate of S. typhimurium in the spleen and a bacteriostatic effect in the liver is found. Hence macrophage activation is probably not very important in the host defense against S. typhimurium.
我们开展这项研究是为了调查巨噬细胞在鼠伤寒沙门氏菌感染期间是否会被激活，若被激活，这些活化的巨噬细胞杀灭鼠伤寒沙门氏菌的速度是否比驻留巨噬细胞更快。给小鼠静脉注射亚致死剂量的鼠伤寒沙门氏菌；在感染约第12天时，肝脏和脾脏中的细菌数量达到最大值。在感染期间，可根据三个标准证明腹腔巨噬细胞被激活，即抑制刚地弓形虫增殖的能力、H2O2产生增加以及Ia抗原表达增加。与驻留巨噬细胞相比，这些活化巨噬细胞在体外对鼠伤寒沙门氏菌的细胞内杀伤率并未增加。为了确定鼠伤寒沙门氏菌在活化小鼠体内的生长情况，使用了一种耐萘啶酸的突变菌株，称为鼠伤寒沙门氏菌510R。鼠伤寒沙门氏菌510活化小鼠和正常小鼠脾脏中突变型鼠伤寒沙门氏菌510R的净生长速率相似。然而，在鼠伤寒沙门氏菌510活化小鼠的肝脏中，注射后3至48小时内鼠伤寒沙门氏菌510R的数量没有变化。在感染初期，特异性抗体的作用可忽略不计，因为在感染的前15天仅检测到低水平的抗体，且抗体滴度高的小鼠脾脏和肝脏中鼠伤寒沙门氏菌510的生长速率与正常小鼠的生长速率无显著差异。这项研究的结果表明，尽管巨噬细胞在鼠伤寒沙门氏菌感染期间会被激活，但这些细胞在体外并未表现出增强的杀菌活性，在体内对脾脏中鼠伤寒沙门氏菌的生长速率没有显著影响，而在肝脏中发现有抑菌作用。因此，巨噬细胞活化在宿主抵御鼠伤寒沙门氏菌的过程中可能不是非常重要。
