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The role of IL-4 in Trypanosoma cruzi infection
Oral Sessions I Pnrasitology International 47 (Suppl.) (1998) 133-281
249
41. Immunology-2 (LeishmaniosisRrypanosomosis)) O-0481
INTERLEUKIN 4 IS A CRUCIAL CYTOKINE IN PARASITEMIA CONTROL OF DURING BRUCEI TRYPANOSOMA GAMBIENSE INFECTION IN MICE
WHYamaguchi
H, Kuriki K, Nagasawa
H, Suzuki N and
0-04R3
THE ROLE OF IL-4 IN TRYPANOSOMA CRUD INFECTION
Hlyama K*, Hamano S*, Nakamura T**, Takimoto H***, Nomoto K**, Tada I*
The Research Center for Protozoan Molecular Immunology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan
*Department of Parasitology, Faculty of Medicine, **Department of Immunology, ***Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
An aim of this study is to clarify the role of interleukin 4 (IL-4) in protective immunity against Trypawsomn brucei gambiettse (T. b. gambieme) infection. C.B-17-+/+ (C.B-17). BALBlc-nulnu (nude) and CB-17scid/scid @CID) mice were infected intraperitoneally (i.p.) with 5,000 of bloodstream forms (BSFs) of trypanosome. Every day for 30 days, parasitemia and packed cell volume (PCV) were examined. Every two days, sera were collected from infected mice to detect IL4, IFN-y and TNF-a production by means of ELISA. The role of IL-4 was examined with use of anti-IL4 (ATCC HB-188, 1 IB II) monoclonal antibody (mAb). BALBlc mice administrated i.p. with anti-IL4 mAb were infected i.p. with 5,000 of BSFs. Parasitemia in peripheral blood was examined daily for 30 days. Levels of parasitemia among three strains of mice were associated with their immunological differences. CB-17 mice showed high resistence to T. b. gambiense infection. Parasitemia in nude mice was persistent but all mice survived more than 60 days after infection. While, SCID mice showed high parasitemia and died within 60 days after infection. IL-4, IFN-y and TNF-a titers increased on early phase of infection in C.B-17 mice. IFN-y titer in nude mice increased on and after 20 days post-infection. While, IL4 titer in nude mice was under the detectable level through the experiment. IL4 and TNF-a titer in SCID mice increased on and after 15 days post-infection. Mice treated i.p. with anti-IL-4 mAb had frequent relapses of parasitemia (anti-IL4 group vs control; p
TryPanosoma cruzi (T. cruzi), a hemoflagellate protozoan parasite, is the causative agent of Chagas’ disease, which is a major health problem in Central and South Americas. The protection against T. cruzi is dependent on both innate and acquired immunity, including several kinds of cell populations. It is well known that cytokines play key roles in regulating immune response. In Leishmaniu major infection, tbe role of IL-4 is clearly shown to deviate the immune system into the Th2 response, which is related to the susceptibility. To elucidate the role of IL-4 in T. cruzi infection, the experiments were performed. Eight-week-old, female, susceptible BALB/c and resistant C57BLJ6 mice were intraperitoneally (i.p.) infected with 1x103 trypomastigotes of T. cruzi. Tulahuen strain. Mice were i.p. injected with 500 ug of anti IL-4 mAb (11 B 11) prior to and during infection. The kinetics of parasitemia and mortality was monitored. Several kinds of cytokines produced from lymphocytes by stimulation with mitogen were measured by ELISA. The parasitemia and mortality in susceptible BALB/c mice were decreased by neutralization of IL-4. Tbe parasitemia was also reduced in resistant C57BU6 mice. However, no significant difference was detected in the production of IFN-7, IL-IO and IL-12 stimulated by mitogen. Now we are preparing purified T. cruzi antigen (Ag) to observe Ag specific response of lymphocytes, and IL-4 deficient mice to analyze the response in the microenvironment free of IL-4. O-0484
KINETIC ANALYSIS OF LIVER NKl.l+ TCELLS IN EXPERIMENTAL TRYPANOSOMA CRUZI INFECIION
NakamuraT*, Hamano S**, Hiyama K**, Takimoto H***, Tada I**, Nomoto K* *Department of Immunology and ***Department of Virology, Medical Institute of Biotegulation, **Department of Parasitology, Faculty of Medicine, Kyushu University, Fukuoka, Japan Polyclonal lymphocyte activation occurs in the early stage of experimental Trypunosoma cruzi infection. The roles of leukocytes, including macrophages, NK cells, T cells and B cells, have been investigated during T. cruri infection, while the role of NKI.l+ T cells, the potential source of IL-4, has not been studied. Here we show the kinetics of NK I. I + T cells and cytokine production during experimental T. cruzi infection. Female C57BL/6 mice, 8-10 weeks of age were intravenously infected with lx103 of bloodstream form of T. cruzi, Tulahuen strain. The lymphocytes in the liver were collected by density gradient centrifugation. The total numbers of lymphocytes were counted and the phenotypes of lymphocytes and its ratio were identified by FACS analysis at several days after infection. Several kinds of cytokines were also measured by ELISA. The total numbers of lymphocytes, especially T cells, in the liver gradually increased during acute infection. However NKl.l + T cell population, which is one of the major lymphocyte populations (about 30 %) in the liver of naive mice, dramatically decreased to I to 3 % on days 14 and 21 after infection. While, serum IL-12 level was kept increased during acute infection. The decrease in NKI .I+ T cells may be related to IL- I2 because IL- 12 downmodulates NKI.1 + T cells during BCG infection. The roles of NKI. I+ T cells and IL12 during T. crud infection are under analysis.
249
41. Immunology-2 (LeishmaniosisRrypanosomosis)) O-0481
INTERLEUKIN 4 IS A CRUCIAL CYTOKINE IN PARASITEMIA CONTROL OF DURING BRUCEI TRYPANOSOMA GAMBIENSE INFECTION IN MICE
WHYamaguchi
H, Kuriki K, Nagasawa
H, Suzuki N and
0-04R3
THE ROLE OF IL-4 IN TRYPANOSOMA CRUD INFECTION
Hlyama K*, Hamano S*, Nakamura T**, Takimoto H***, Nomoto K**, Tada I*
The Research Center for Protozoan Molecular Immunology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan
*Department of Parasitology, Faculty of Medicine, **Department of Immunology, ***Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
An aim of this study is to clarify the role of interleukin 4 (IL-4) in protective immunity against Trypawsomn brucei gambiettse (T. b. gambieme) infection. C.B-17-+/+ (C.B-17). BALBlc-nulnu (nude) and CB-17scid/scid @CID) mice were infected intraperitoneally (i.p.) with 5,000 of bloodstream forms (BSFs) of trypanosome. Every day for 30 days, parasitemia and packed cell volume (PCV) were examined. Every two days, sera were collected from infected mice to detect IL4, IFN-y and TNF-a production by means of ELISA. The role of IL-4 was examined with use of anti-IL4 (ATCC HB-188, 1 IB II) monoclonal antibody (mAb). BALBlc mice administrated i.p. with anti-IL4 mAb were infected i.p. with 5,000 of BSFs. Parasitemia in peripheral blood was examined daily for 30 days. Levels of parasitemia among three strains of mice were associated with their immunological differences. CB-17 mice showed high resistence to T. b. gambiense infection. Parasitemia in nude mice was persistent but all mice survived more than 60 days after infection. While, SCID mice showed high parasitemia and died within 60 days after infection. IL-4, IFN-y and TNF-a titers increased on early phase of infection in C.B-17 mice. IFN-y titer in nude mice increased on and after 20 days post-infection. While, IL4 titer in nude mice was under the detectable level through the experiment. IL4 and TNF-a titer in SCID mice increased on and after 15 days post-infection. Mice treated i.p. with anti-IL-4 mAb had frequent relapses of parasitemia (anti-IL4 group vs control; p
TryPanosoma cruzi (T. cruzi), a hemoflagellate protozoan parasite, is the causative agent of Chagas’ disease, which is a major health problem in Central and South Americas. The protection against T. cruzi is dependent on both innate and acquired immunity, including several kinds of cell populations. It is well known that cytokines play key roles in regulating immune response. In Leishmaniu major infection, tbe role of IL-4 is clearly shown to deviate the immune system into the Th2 response, which is related to the susceptibility. To elucidate the role of IL-4 in T. cruzi infection, the experiments were performed. Eight-week-old, female, susceptible BALB/c and resistant C57BLJ6 mice were intraperitoneally (i.p.) infected with 1x103 trypomastigotes of T. cruzi. Tulahuen strain. Mice were i.p. injected with 500 ug of anti IL-4 mAb (11 B 11) prior to and during infection. The kinetics of parasitemia and mortality was monitored. Several kinds of cytokines produced from lymphocytes by stimulation with mitogen were measured by ELISA. The parasitemia and mortality in susceptible BALB/c mice were decreased by neutralization of IL-4. Tbe parasitemia was also reduced in resistant C57BU6 mice. However, no significant difference was detected in the production of IFN-7, IL-IO and IL-12 stimulated by mitogen. Now we are preparing purified T. cruzi antigen (Ag) to observe Ag specific response of lymphocytes, and IL-4 deficient mice to analyze the response in the microenvironment free of IL-4. O-0484
KINETIC ANALYSIS OF LIVER NKl.l+ TCELLS IN EXPERIMENTAL TRYPANOSOMA CRUZI INFECIION
NakamuraT*, Hamano S**, Hiyama K**, Takimoto H***, Tada I**, Nomoto K* *Department of Immunology and ***Department of Virology, Medical Institute of Biotegulation, **Department of Parasitology, Faculty of Medicine, Kyushu University, Fukuoka, Japan Polyclonal lymphocyte activation occurs in the early stage of experimental Trypunosoma cruzi infection. The roles of leukocytes, including macrophages, NK cells, T cells and B cells, have been investigated during T. cruri infection, while the role of NKI.l+ T cells, the potential source of IL-4, has not been studied. Here we show the kinetics of NK I. I + T cells and cytokine production during experimental T. cruzi infection. Female C57BL/6 mice, 8-10 weeks of age were intravenously infected with lx103 of bloodstream form of T. cruzi, Tulahuen strain. The lymphocytes in the liver were collected by density gradient centrifugation. The total numbers of lymphocytes were counted and the phenotypes of lymphocytes and its ratio were identified by FACS analysis at several days after infection. Several kinds of cytokines were also measured by ELISA. The total numbers of lymphocytes, especially T cells, in the liver gradually increased during acute infection. However NKl.l + T cell population, which is one of the major lymphocyte populations (about 30 %) in the liver of naive mice, dramatically decreased to I to 3 % on days 14 and 21 after infection. While, serum IL-12 level was kept increased during acute infection. The decrease in NKI .I+ T cells may be related to IL- I2 because IL- 12 downmodulates NKI.1 + T cells during BCG infection. The roles of NKI. I+ T cells and IL12 during T. crud infection are under analysis.