Toxoplasma gondii: mechanism of resistance to complement-mediated killing

• Published in: The Journal of immunology (1950) Vol. 142; no. 3; pp. 940 - 947
• Main Authors: Fuhrman, SA, Joiner, KA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-02-1989
• Subjects: Animals; Blood - immunology; Blood - parasitology; Complement C3 - isolation & purification; Complement C3 - metabolism; Complement C9 - metabolism; Complement Pathway, Alternative; Complement System Proteins - immunology; Complement System Proteins - metabolism; Complement System Proteins - physiology; Cytotoxicity, Immunologic; Humans; Immunity, Innate; Immunization; Macrophage-1 Antigen; Receptors, Complement - analysis; Toxoplasma - growth & development; Toxoplasma - immunology; Toxoplasma - metabolism; Toxoplasma gondii
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.142.3.940

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.