Murine natural resistance to Trypanosoma lewisi involves complement component C3 and radiation-resistant, silica dust-sensitive effector cells.
The phenomenon of natural (innate) resistance is exemplified by the solid resistance of mice to infection with the rat-specific Trypanosoma lewisi. We provide more information about the mechanism of resistance in this model system. Resistance was not diminished in aged mice or reduced by ionizing radiation or splenectomy. There was no difference in resistance of C5-deficient mice (B10.D2/oSn and AKR) compared with their normocomplementemic counterparts (B10.D2/nSn and C57BL/6). Treatment of mice with cobra venom factor resulted in greatly prolonged survival of T. lewisi in mice. Combined treatment of mice with cobra venom factor and silica dust resulted in not only prolonged survival but also considerable intravascular growth of the parasite and resultant death of the mice. T. lewisi cells from irradiated donor rats, or after surface coat removal with trypsin, were eliminated by inoculated mice more efficiently than were parasites acquired from normal rats. Incubation of trypanosomes obtained from irradiated rats in normal rat serum restored their resistance to rapid elimination. From the results of these studies and other recent investigations, we have concluded that murine resistance to T. lewisi involves activation and binding of C3b by uncoated trypanosomes and concomitant participation of radiation-resistant, silica dust-sensitive effector cells (probably macrophages and neutrophils), and rat plasma proteins, integrated into the trypanosome surface coat, stabilize the coat, make it less susceptible to removal when the trypanosome is present in the mouse bloodstream, and thus delay exposure of underlying molecules (receptors?) that activate murine C3.
Albright
J W
JW
Albright
J F
JF
D000818:Animals; D003176:Complement C3 / Q000276:immunology*; D004391:Dust; D007113:Immunity, Innate; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology*; D013045:Species Specificity; D014350:Trypanosoma lewisi / Q000276:immunology / Q000472:pathogenicity*; D014352:Trypanosomiasis / Q000276:immunology*
D003176:Complement C3; D004391:Dust; D012822:Silicon Dioxide