Elucidation of the role of host immune system in antimalarial mechanism of action

There are several therapeutic drugs (antimalarial drugs) for the treatment of malaria, depending on the stage of infection, and their effectiveness has been demonstrated. There are many therapeutic drugs, such as chloroquine, mefloquine, and artemisinin, especially for the red end stage when symptoms of malaria appear. Generally, these drugs have the effect of directly killing malaria parasites, and it is believed that this effect is effective in the treatment of malaria. On the other hand, it was found that chloroquine had no effect on red end stage malaria in some immunodeficient mice. This suggests that the host immune system is essential for the mechanism of action of antimalarial drugs (antimalarial therapeutic effect) during the red end phase of mouse malaria. In this study, based on our findings, the role of the host immune system in the mechanism of action of antimalarial drugs in vivo will be verified. It will also verify the mechanism of emergence of antimalarial drug-resistant protozoa in vivo and its drug resistance mechanism. This year, the study attempted to identify the host immune system that is essential for the integrated action of anti-malarial drugs in vivo. As a result, 1) administration of chloroquine to non-lethal P. yoelii (PyXNL) red end stage infection reduces parasitemia in mice lacking an adaptive immune system. However, when parasitemia disappeared at the microscopic level and chloroquine administration was discontinued, parasitemia reappeared. 2) In mice lacking B cells, parasitemia was reduced by chloroquine against PyXNL red end stage infection. However, when parasitemia disappeared at the microscopic level and chloroquine administration was discontinued, parasitemia reappeared. 3) Antibody-deficient mice showed no effect of chloroquine administration on PyXNL red end stage infection (almost no reduction in parasitemia). These results suggest that chloroquine exerts its effect in vivo in the presence of antibodies, and that the effect may require the presence of the host’s adaptive immune system, especially B cells.

Project details

Basic Science
Drug Resistance

Apr 2020 — Mar 2024

$152,708

Japan