Cooperative action of complement component C3 and phagocytic effector cells in innate murine resistance to Trypanosoma lewisi.
Mice display strong natural resistance to the rat-specific Trypanosoma lewisi. Intravenously injected intact T. lewisi parasites were eliminated by mice within 18 to 24 h. In comparison, "nude" T. lewisi organisms lacking the surface coat were rapidly and totally cleared from the bloodstream within 2 h postinoculation. Similarly, in vitro-cultivated trypanosomes were readily eliminated by mice with the conspicuous absence of a lag phase. Elimination of nude T. lewisi, like that of intact trypanosomes, required murine complement component C3. Splenectomy of mice did not affect their ability to eliminate T. lewisi. However, C3 depletion with cobra venom factor rendered splenectomized mice susceptible to this rat trypanosome; in these mice, T. lewisi established prolonged and frequently fatal infections. Beige mice were able to efficiently eliminate T. lewisi. But combined treatments of beige (bg/bg) and heterozygous (bg/+) mice with cobra venom factor and silica dust, or normal rat serum and silica dust, incapacitated the natural resistance of these mice to T. lewisi. Such combined treatments of beige and control mice resulted in fulminating parasitemias and death of the animals. Altogether, the results of the present studies indicate that T. lewisi elimination by mice requires the following: exposure of C3 acceptors on the surface of the parasites; activation of murine C3, probably via the alternative complement pathway; and destruction of the C3b-coated parasites by their interaction with C3b receptor-bearing, phagocytic effector cells that are abundant in the spleen and sensitive to silica dust.
D000818:Animals; D001790:Blood Physiological Phenomena; D003176:Complement C3 / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000502:physiology*; D012822:Silicon Dioxide / Q000494:pharmacology; D013156:Splenectomy; D014350:Trypanosoma lewisi / Q000276:immunology*
D003176:Complement C3; D004546:Elapid Venoms; C016310:cobra venom factor; D012822:Silicon Dioxide