Dr. Yasuhiro Suzukis Immunology LabResearch Interests:My laboratory has been investigating the mechanism of host-pathogen interactions in infection with Toxoplasma gondii, an obligate intracellular protozoan parasite. Our recent focus of research is the molecular immunopathogenesis of cerebral toxoplasmosis. Toxoplasmic encephalitis (TE) has been a major opportunistic infectious disease in immunocompromised patients, such as those with AIDS and organ transplant recipients. In addition, TE is an excellent model for analyzing the mechanism of host defense in the brain. We have developed murine models of TE and found three factors critical in determining the host resistance to this disease. These are: IFN-g-mediated immune response, the genetic background of the host, and the strain of T. gondii. We are trying to obtain understanding of the molecular basis of host resistance to development of TE, by defining how the IFN-g-mediated immune response functions in the brain and how the genetic background of the host and the strain of T. gondii affect the immune response. Selected Publications:Suzuki Y, Joh K and Kobayashi A. Tumor necrosis factor-independent protective effect of recombinant IFN-g against acute toxoplasmosis in T cell-deficient mice. J Immunol 147:2728-2733, 1991. Suzuki Y, Joh K, Conley FK and Remington JS. A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice. Immunology 74:732-739, 1991. Orellana MA, Suzuki Y, Araujo F and Remington JS. Role of beta interferon in resistance to Toxoplasma gondii infection. Infect Immun 59:3287-3290, 1991. Makioka A, Suzuki Y and Kobayashi A. Recognition of tachyzoite and bradyzoite antigens of Toxoplasma gondii by infected hosts. Infect Immun 59:2763-2766, 1991. Suzuki Y, Kobayashi A, Nishizawa T, Inagawa H, Morikawa A, Soma GI and Mizuno D. Homeostasis as regulated by activated macrophage. VI. Protective effect of LPSw (a lipopolysaccharide from wheat flour) against acute infection with Toxoplasma gondii in mice. Chem Pharm Bull 40:1266-1267, 1992. Freund Y, Sgarlato G, Jacob CO, Suzuki Y and Remington JS. Polymorphisms in the tumor necrosis factor a (TNF-a) gene correlate with murine resistance to development of toxoplasmic encephalitis and with levels of TNF-a mRNA in infected brain tissue. J Exp Med 175:683-688, 1992. Asai T, Mizuno F, Kojima S, Takeuchi T, Kobayashi A and Suzuki Y. High correlation in antibody titers between the Sabin-Feldman dye test and an enzyme-linked immunosorbent assay detecting immunoglobulin G antibodies to the nucleoside triphosphate hydrolase of Toxoplasma gondii. J Clin Microbiol 30:1291-1293, 1992. Suzuki Y and Remington JS. Toxoplasmosis. In: Encyclopedia of Immunology, Raitt IM and Delves PJ eds, Academic Press, pp.1495-1496, 1992. Freund YR, Suzuki Y and Remington JS. Is TNF beneficial or deleterious in resistance to toxoplasmic encephalitis? (reply) Parasitol Today 8:335-336, 1992. Watanabe H, Suzuki Y, Makino M and Fujiwara M. Toxoplasma gondii: Induction of toxoplasmic encephalitis in mice with chronic infection by inoculation of a murine leukemia virus inducing immunodeficiency. Exp Parasitol 76:39-45, 1993. Suzuki Y, Orellana MA, Conley FK and Remington JS. Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection in mice. Infect Immun 61:2284-2288, 1993. Suzuki Y and Remington JS. Toxoplasmic encephalitis in AIDS patients and experimental models for study of the disease and its treatment. Res Immunol 144:66-67, 1993. Suzuki Y and Joh K. Effect of strain of Toxoplasma gondii on development of toxoplasmic encephalitis in mice treated with antibody to interferon-gamma. Parasitol Res 80:125-130, 1994. Suzuki Y and Remington JS. Toxoplasmic encephalitis in AIDS patients and experimental models for study of the disease and its treatment. Res Immunol 144:66-67, 1993. Suzuki Y. Factors responsible for development of toxoplasmic encephalitis in immunocompromised hosts. NATO ASI Series 78:153-155, 1993. Suzuki Y, Yang Q, Conley FK, Abrams JS and Remington JS. Antibody against interleukin-6 reduces inflammation and numbers of cysts in brains of mice with toxoplasmic encephalitis. Infect Immun 62:2773-2778, 1994. Suzuki Y, Joh K, Kwon OC, Yang Q, Conley FK and Remington JA. A gene(s) in the D/L region of the MHC class I antigens but not the TNF-a gene determines development of toxoplasmic encephalitis in mice. J Immunol 153:4649-4654, 1994. Suzuki Y, Yang Q and Remington JS. Genetic resistance against acute toxoplasmosis depends on the strain of Toxoplasma gondii. J Parasitol 81:1032-1034, 1995. Suzuki Y, Wong, SW, Grumet FC, Fessel J, Montoya JG, Zolopa AR, Portimore A, Schumacher-Perdreau F, Schrappe M, Koppen S, Ruf B, Brwon BW and Remington JS. Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients. J Infect Dis 173:265-268, 1996. Araujo FG, Suzuki Y and Remington JS. Use of rifabutin in combination with atovacone, clindamycin, pyrimethamine, or sulfadiazine for treatment of toxoplasmic encephalitis. Eur J Clin Microbiol Infect Dis 15:394-397, 1996. Minamidani M, Tanaka J and Suzuki Y. Pathomechanism of cerebral hypoplasia in experimental toxoplasmosis in murine fetuses. Early Human Develop 44:37-50, 1996. Liesenfeld O, Kosek J, Remington JS and Suzuki Y. Association of CD4+ T cell-dependent, interferon-g-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 184: 597-607, 1996. Hunter CA, Suzuki Y, Subauste CS and Remington JS. Cells and cytokines in resistance to Toxoplasma gondii. Cur. Topics Microbiol Immunol 219:113-125, 1996. Suzuki Y, Yang Q, Yang, S, Nguyen N, Lim S, Liesenfeld O, Kojima T and Remington JS. IL-4 is protective against development of toxoplasmic encephalitis. J Immunol 157:2564-2569, 1996. Suzuki Y, Rani S, Liesenfeld O, Kojima T, Lim S, Nguyen TA, Dalrymple SA, Murray R and Remington JS. Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice. Infect Immun 65:2339-2345, 1997. Liesenfeld O, Kosek JC and Suzuki Y. Gamma interferon induces Fas-dependent apoptosis of Peyer's patch T cells in mice following peroral infection with Toxoplasma gondii. Infect Immun 65:4682-4689, 1997. Suzuki Y. Cells and cytokines in the central nervous system. In: In Defense of the Brain. Remington JS and Peterson PK eds. Blackwell Scientific pp. 56-73, 1997. Yap GS, Scharton-Kersten T, Ferguson DJP, Howe D, Suzuki Y and Sher A. Partially protective vaccination permits the development of latency in a normally virulent strain of Toxoplasma gondii. Infect Immun 66: 4382-4388, 1998. Ellis Neyer L, Remington JS and Suzuki Y. Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to Concanavalin A following peroral infection with Toxoplasma gondii. Parasite Immunol 20:573-581, 1998. Suzuki Y and Remington JS. Toxoplasmosis. In: Encyclopedia of Immunology, Second Edition. Raitt IM and Delves PJ eds. Academic Press, pp.2383-2384, 1998 Liesenfeld O, Kang, H, Park D, Nguyen TA, Parkhe CV, Watanabe H, Abo T, Sher A, Remington JS and Suzuki Y. TNF-a, nitric oxide, and IFN-g are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 22:365-376, 1999. Liesenfeld O, Kosek J, Remington JS and Suzuki Y. Interferon-gamma induces necrosis in the small intestine of mice following peroral infection with Toxoplasma gondii. In: Induction and modulation of gastrointestinal inflammation, Kluwer Academic Publishers, pp.209-213, 1999. Suzuki, Y. Genes, cells and cytokines in resistance against development of toxoplasmic encephalitis. Immunobiology 201:255-271, 1999. Li S, Maine G, Suzuki Y, Araujo FG, Galvan G, Remington JS and Parmley S. Serodiagnosis of recently acquired Toxoplasma gondii infection with a recombinant antigen. J Clin Microbiol 38:179-184, 2000. Kang H, Remington JS, and Suzuki, Y. Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-g, TNF-a and inducible nitric oxide synthase. J Immunol 164:2629-2634, 2000. Suzuki Y, Sher A, Yap G, Park D, Ellis Neyer L, Liesenfeld O, Fort M, Kang H and Gufwoli E. IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J Immunol 154:5375-5382, 2000. Suzuki Y, Kang H, Parmley S, Lim S, and Park D. Induction of tumor necrosis factor-a and inducible nitric oxide synthase fails to prevent toxoplasmic encephalitis in the absence of interferon-g in genetically resistant BALB/c mice. Microbes Infect 2:455-462, 2000. Li S, Galvan G, Araujo FG, Suzuki Y, Remington JS, and Parmley S. Serodiagnosis of recently acquired infection with Toxoplasma gondii using ELISA with a combination of recombinant antigens. Clin Diagn Lab Immunol 7:781-787, 2000. Suzuki Y, Ramirez R, Press C, Li S, Parmley S, Thulliez P, and Remington JS. Detection of IgM antibodies to P35 antigen of Toxoplasma gondii for serodiagnosis of recently acquired infection in pregnant women. J Clin Microbiol 38:3967-3970, 2000. Khan AA, Slifer TR, Araujo FG, Suzuki Y, and Remington, JS. Protection against lopopolysaccharide (LPS)-induced death by fluoroquinolones. Antimicrob Agents Chemother 44:3169-3173, 2000. Suzuki, Y. and Remington JS. Immunopathogenesis of CNS toxoplasmosis. In: New Concepts on the Immunopathogenesis of CNS Infections. Remington JS and Peterson PK eds. Blackwell Science, pp. 143-162, 2000. Araujo MI, Bliss SK, Suzuki Y, Denkers EY, and Pearce EJ. IL-12 promotes liver pathology and death in mice co-infected with Schistosoma mansoni and Toxoplasma gondii. Infect Immun 69:1454-1462, 2001. Kang H, and Suzuki Y. Requirement of non-T cells that produce interferon-gamma for prevention of reactivation of Toxoplasma gondii infection in the brain. Infect Immun 69:2920-2927, 2001. Grigg, ME, Bonnefoy, S., Hehl, A. B., Suzuki, Y*, and Boothroyd, J. C*. Success and virulence in Toxoplasma as the results of sexual recombination between two distinct ancectries. Science 294:161-165, 2001. *joint corresponding authors. Liesenfeld, O, Nguyen TA, Pharke C, and Suzuki Y. Importance of gender and sex hormones in regulation of susceptibility of the small intestine to peroral infection with Toxoplasma gondii tissue cysts. J Parasitol 87:1491-1493, 2001. Johnson J, Suzuki Y, Mack D, Mui E, Estes R, David C, Skamene E, Forman J, and McLeod R. Genetic analysis of influences on survial following Toxoplasma gondii infection. Int J Parasitol 32:179-185, 2002. Suzuki, Y. Host resistance in the brain against Toxoplasma gondii. J Infect Dis 185:S58-65, 2002. |