title: Splenic macrophage function in early syphilitic infection is complex. Stimulation versus down-regulation.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of Minnesota, Duluth 55812.
authors.forename: M A
authors.initials: MA
authors.lastname: Tomai
authors.forename: T J
authors.initials: TJ
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D013154:Spleen / Q000166:cytology; D013587:Syphilis / Q000276:immunology*; D013733:Testicular Diseases / Q000382:microbiology; D014210:Treponema pallidum
chemical_list: D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D011453:Prostaglandins; D003208:Concanavalin A; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin