Induction of activated macrophages in C3H/HeJ mice by avirulent Salmonella.
A single injection of viable Salmonella typhimurium SL3235, an avirulent organism blocked in the aromatic pathway, induced the generation of activated peritoneal macrophages in three different C3H mouse strains, including macrophage-defective C3H/HeJ mice. Macrophages obtained from immunized mice were cytotoxic for B16 melanoma cells, P815 mastocytoma cells, and TU-5 fibrosarcoma cells and microbicidal in vitro for the obligate, intracellular, protozoan parasite Leishmania major. The capacity of live SL3235 to activate C3H/HeJ macrophages contrasts with the failure of live Bacillus Calmette-Guérin to induce activated macrophages in this mouse strain. Although viable SL3235 were capable of fully activating cells of both normal and defective mice, a dose-dependent difference was observed in the number of organisms necessary for induction of tumoricidal macrophages in C3HeB/FeJ (normal) and C3H/HeJ (defective) animals. As few as 80 viable SL3235 were capable of activating C3HeB/FeJ macrophages whereas 5 X 10(4) organisms were required to activate C3H/HeJ macrophages. Maximal macrophage activation occurred 7 to 10 days after SL3235 inoculation in C3H/HeJ and C3HeB/FeJ mice. Acetone-killed cells of SL3235 had some but not all of the activity of the living Salmonella. A single in vivo injection of the nonviable preparation resulted in the induction of tumoricidal macrophages in C3HeB/FeJ but not in C3H/HeJ mice, even when tested over a wide dosage range. Injection of acetone-killed cells of SL3235 did, however, result in a population of primed macrophages in C3H/HeJ mice, as explanted cells could be induced to express activated macrophage effector activities after additional treatment in vitro with either LPS or IFN-gamma. Thus, in vivo administration of viable SL3235 is, by itself, capable of eliciting the full series of steps required for activation of C3H/HeJ macrophages, whereas killed SL3235 only provides signals sufficient to prime these defective macrophages for further activation in vitro. AI 15613
Schafer
R
R
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140.
Nacy
C A
CA
Eisenstein
T K
TK
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007700:Kinetics; D007896:Leishmaniasis / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H / Q000235:genetics / Q000276:immunology*; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity*; D012513:Sarcoma, Experimental / Q000276:immunology; D014774:Virulence
D001500:BCG Vaccine