BCG-induced granuloma formation in murine tissues.
BCG infection of mice provides a convenient model to study natural and cellular immunity to mycobacteria and the mechanisms of granuloma formation and repair. We have used a range of macrophage (M phi) membrane molecules and secretory products to investigate resident M phi-pathogen interactions and T lymphocyte-dependent recruitment and activation of M phi in different tissues of immature, normal adult and gamma interferon deficient animals. In situ hybridization (ISH), RT-PCR and immunocytochemical analysis of M phi gene and product expression have been correlated with in vitro study of endocytic and secretory activity in which biogel polyacrylamide bead-elicited peritoneal M phi are exposed to Th1 and Th2 cytokines, LPS, BCG and other stimuli. The role of resident and newly recruited M phi responding to BCG in liver, spleen, lung and brain has been defined by means of antigen markers expressed by M phi (F4/80, 7/4, CR3, macrosialin, sialoadhesin and scavenger receptor) and/or T and B lymphoid cells (MHC Class II, CD4, CD8, B220). Heterogeneity in M phi secretory activity was revealed by ISH analysis of lysozyme, TNF-alpha, IL-1 IL-6 and MCP-1, by in vitro assay of NO and superoxide anion production, and by RT-PCR studies of Th1 (interferon gamma) and Th2 (IL-4, IL-13, IL-10) lymphokine mRNA in tissues. Our studies confirm the importance of interferon gamma as a critical mediator of host resistance to mycobacterial infection and raise intriguing questions in regard to T cell and M phi functional heterogeneity in distinct tissue microenvironments.
Gordon
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S
Sir William Dunn School of Pathology, University of Oxford, England.
Keshav
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S
Stein
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M
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D004195:Disease Models, Animal; D006099:Granuloma / Q000209:etiology*; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity*
D000954:Antigens, Surface