An animal model of chronic infection of malaria parasites, Plasmodium berghei NK65

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09670267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 寄生虫学(含医用動物学)
• Research Institution: Nagasaki University
• Principal Investigator: NAKAZAWA Shusuke Institute of Tropical Medicine, Nagasaki University, Research Associate, 熱帯医学研究所, 助手 (20180268)
• Co-Investigator(Kenkyū-buntansha): KANBARA Hiroji Institute of Tropical Medicine, Nagasaki University, Professor, 熱帯医学研究所, 教授 (20029789) ; UEMURA Haruki Institute of Tropical Medicine, Nagasaki University, Assistant Professor, 熱帯医学研究所, 講師 (60184975)
• Project Period (FY): 1997 – 1998
• Keywords: malaria / a chronic infection / an animal model of chronic malaria / Plasmodium berghei NK65 / recrudescences / an adoptive spleen cell transfer / a protective immunity / pathogenic reactions

Research Abstract

A mouse model of a chronic infection with malaria parasites, Plasmodium berghei NK65, was established by suppression of recrudescent parasitemias four times with standard dose of chloroquine treatment. Mice immunized by the methods above were found to develop protective immunity against parasites. Throughout the infectious course from the 2nd recrudescence to the end of observation, IgG2a was predominat among IgG subclasses specific for parasite antigens. Number of spleen T cells, CD4ィイD1+ィエD1 and γδ T cells in particular, was gradually increased with showing a fluctuation parallel to parasitemia during the immunization period and finally reached to 5 times of the number of normal spleen T cells. Then, it was decreased to be 2 times of the number of normal spleen T cells and was again increased extremely after challenge infection, albeit for low parasitemias. Kinetics of cytokines was similar to that of spleen T cells. IL-12 serum level, however, showed a big surge just after infection followed by small peaks associated with spleen T cell number. IL-10 level in the supernatant of spleen cell cultures was increased when INF-γ and TNF-α levels were decreased and vice versa during the latter half of immunization period and thereafter. Depletion of CD8ィイD1+ィエD1T cells and γδ T cells by injection of anti-T cells antibodies to mice with chronic infections gave them no or a slight effect on their parasitemias. On the contrary, CD4ィイD1+ィエD1T cell depletion abrogated the protection. The mice treated with anti-CD4ィイD1+ィエD1T cell antibody demonstrated increasing parasitemias and died. Periphral blood immunoglobulin levels were decreased during the treatment. Adoptive spleen cell transfer experiment using mice with chronic infection as donors and naive mice as recipients revealed that mice transfused with immune spleen cells from donors and challenged 24 hours after transfusion died earlier with low parasitemias compared with control mice. These results suggest that a mouse model of a chronic infection should be a useful tool for dissecting immune status in chronic malaria.