Developmental biotechnological and molecular immunological analysis of host defense mechanisms against protozoan infection

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Protozoan parasites are most important causative of infectious diseases in the world. The subjectives of this study have focused on the prevention of protozoan diseases through the studies on biological substances and products derived from protozoa themselves, as well as on host defense mechanisms. Genetically modified animals such as transgenic mice and knockout mice are known to be powerful tools for analysis of gene function in vivo.(1) Identification of specific molecules from Toxoplasma gondii, Babesia sp., Trypanosoma sp., Neospora caninum, Cryptosoridium parvum using molecular biological techniques.(2) Localization of immunogenic molecules from protozoan parasites using IFA, confocal leser microscope, immuno-EM.(3) Analysis of host immune responses using knockout mice as well as transgenic mice such as SAG-1 transgenic mouse, IFN-γ knockout mouse, scavenger receptor (SR) knockout mouse and TNF-α knockout mouse.SAG-1 (p30), the major surface protein of Toxoplasma gondii, is consi … More dered as an important ligand in the process of host cell invasion. To analyze the mechanism of host cell irivasion and immune response in toxoplasmosis, we have established transgenic mice carrying p30 for the first time in the world. Moreover, many kind of knockout mice deficient in cytokines or receptors have been used for analysis of the host defense mechanisms against protozoan infection in our research center.It was found that among surface molecules of antigen presenting cells (APC), class II, CD80 and CD86 have a crucial role for protective immune responses against protozoan infection. Although expression level of CD28 on T cells was not changed after infection, effective molecules to activate T cells, that is class II, CD80 and CD86 on the APC, were significantly detectable with high expression. SAG-1 (p30) is considered as an important ligand in the process of host cell invasion. If this protein is produced by host cells and interfere with that of parasites, then the host will become resistant to parasite invasion. Or, it may become more susceptible to infection due to the lack of immune response against p30 antigen. We have obtained several P30-founder mice expressing the gene product and transmitting the gene to the next generation, by using F1 (C57BL/6J x C3H/He) embryos. As far as we are aware, this is the first transgenic mice bearing a protozoan gene derived from T. gondii. We found that P30 molecule is one of important trigger to introduce the host immune responses against Toxoplasma infection. Furthermore, apoptosis of host cells is one of escape mechanisms of protozoan parasite against host protective immunity. Less