Toxoplasma gondii: mechanism of resistance to complement-mediated killing.
Tachyzoites of the obligate intracellular protozoan Toxoplasma gondii are resistant to lysis in non-immune human serum. We have examined the mechanism of this serum resistance in RH and P strain organisms, which differ markedly in virulence, but are equally resistant to serum killing. Rapid, but limited, activation of the alternative complement pathway occurred in non-immune human serum, with deposition of equivalent amounts of C3 on the two strains. C component C3 bound covalently to parasite acceptor molecules via an ester linkage. The predominant form of C3 was iC3b which cannot participate in formation of a lytic C5b-9 complex. Multiple membrane constituents of the tachyzoite of T. gondii may serve as acceptors for the limited amount of C3 deposited during incubation in non-immune serum. When tachyzoites were presensitized with the lytic anti-p30 mAb 7B8, new amide-linked C3-acceptor complexes formed. Nearly equivalent C3 binding but a threefold enhancement of 125I-C9 binding occurred when mAb 7B8 pre-sensitized tachyzoites were compared to native organisms. These results indicate that tachyzoites of T. gondii are serum resistant because of failure to activate C efficiently. Presensitization with a lytic mAb alters the site of complement deposition and augments C5b-9 formation.
Fuhrman
S A
SA
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Joiner
K A
KA
D000818:Animals; D001769:Blood / Q000276:immunology / Q000469:parasitology; D003176:Complement C3 / Q000302:isolation & purification / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement / Q000032:analysis; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism
D003176:Complement C3; D003186:Complement C9; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D003165:Complement System Proteins