Tomai M A, Fitzgerald T J
Department of Medical Microbiology and Immunology, School of Medicine, University of Minnesota, Duluth 55812.
J Immunol. 1991 May 1;146(9):3171-6.
Macrophages are important regulatory cells that can both stimulate and down-regulate various immune functions. During syphilitic infection, these cells phagocytize, kill, and lyse Treponema pallidum. They also modulate early T cell activation by decreasing IL-2 production through secretion of PG. This report focuses on additional complexities of macrophage regulation. Non-adherent splenic cells were stimulated with Con A to induce IFN-gamma synthesis. High levels were detected in preparations from normal rabbits and much lower levels in preparations from infected rabbits. The organisms also readily stimulated IL-1 synthesis by adherent spleen preparations from normal but not from infected rabbits. When indomethacin was added to these latter preparations, this IL-1 defect was reversed, implicating PG in this down-regulation. Spleen cells were obtained from normal rabbits and from rabbits infected testicularly for 9 to 12 days. Infection elevated basal levels of class II Ia Ag on adherent cells. In addition, macrophage Ia expression was increased during 4 days of in vitro incubation with treponemes. Non-adherent spleen cells from infected animals inhibited two different macrophage functions. First, culture filtrates obtained after 48 h of incubation contained a soluble factor that subsequently decreased LPS-induced IL-1 synthesis. Second, when macrophages were co-incubated with non-adherent cells, treponemal stimulation of macrophage Ia expression was inhibited; this inhibition was reversed by indomethacin implicating prostaglandins in this down-regulation. In further experiments an exogenous source of IFN-gamma was incubated with adherent cells from infected rabbits. This stimulated macrophage function as shown by increased IL-1 synthesis and Ia expression and decreased PGE2 secretion. Results are discussed in terms of the complexities of immunoregulation by macrophages during syphilitic infection.
巨噬细胞是重要的调节细胞，既能刺激也能下调各种免疫功能。在梅毒感染期间，这些细胞吞噬、杀死并裂解梅毒螺旋体。它们还通过分泌前列腺素减少白细胞介素 -2 的产生来调节早期 T 细胞活化。本报告聚焦于巨噬细胞调节的其他复杂性。用刀豆蛋白 A 刺激非贴壁脾细胞以诱导干扰素 -γ 合成。在正常兔的细胞制剂中检测到高水平的干扰素 -γ，而在感染兔的细胞制剂中水平低得多。这些病原体还能轻易刺激正常兔而非感染兔的贴壁脾细胞制剂合成白细胞介素 -1。当将吲哚美辛添加到这些后者的制剂中时，这种白细胞介素 -1 缺陷得以逆转，表明前列腺素参与了这种下调作用。从正常兔和睾丸感染 9 至 12 天的兔中获取脾细胞。感染提高了贴壁细胞上 II 类 Ia 抗原的基础水平。此外，在与梅毒螺旋体进行 4 天体外孵育期间，巨噬细胞 Ia 表达增加。来自感染动物的非贴壁脾细胞抑制两种不同的巨噬细胞功能。首先，孵育 48 小时后获得的培养滤液含有一种可溶性因子，该因子随后会降低脂多糖诱导的白细胞介素 -1 合成。其次，当巨噬细胞与非贴壁细胞共同孵育时，梅毒螺旋体对巨噬细胞 Ia 表达的刺激受到抑制；这种抑制作用被吲哚美辛逆转，表明前列腺素参与了这种下调作用。在进一步的实验中，将外源性干扰素 -γ 与感染兔的贴壁细胞一起孵育。这刺激了巨噬细胞功能，表现为白细胞介素 -1 合成增加、Ia 表达增加以及前列腺素 E2 分泌减少。根据梅毒感染期间巨噬细胞免疫调节的复杂性对结果进行了讨论。
