The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection.
Granuloma formation in the liver of mice infected with BCG coincides with local TNF synthesis. Injection of rabbit anti-TNF antibody, after 1 or 2 weeks of infection, dramatically interferes with the development of granulomas (both in number and size, large epithelioid cells failing to appear) and subsequent mycobacterial elimination. Furthermore, fully developed BCG granulomas, after 3 weeks of infection, rapidly regress after anti-TNF treatment. Antibody treatment also prevents or suppresses accumulation of TNF mRNA and protein, which resumes after disappearance of the antibody. Peritoneal macrophages exposed to TNF transiently accumulate TNF mRNA, and show an enhanced increase in TNF mRNA in response to gamma interferon. We propose that TNF released from macrophages in the microenvironment of developing granulomas is involved in a process of autoamplification: acting in an autocrine or paracrine way, it enhances its own synthesis and release, thus favoring further macrophage accumulation and differentiation leading to bacterial elimination.
Kindler
V
V
Department of Pathology, University of Geneva, Centre Medical Universitaire, Switzerland.
Sappino
A P
AP
Grau
G E
GE
Piguet
P F
PF
Vassalli
P
P
D000818:Animals; D000917:Antibody Formation; D015152:Blotting, Northern; D006099:Granuloma / Q000503:physiopathology*; D007158:Immunologic Techniques; D008107:Liver Diseases / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014376:Tuberculosis / Q000503:physiopathology / Q000662:veterinary*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha