Elucidation of novel malaria infection defense mechanism based on understanding of intestinal environment

The involvement of intestinal bacteria in malaria infection has attracted a great deal of attention internationally, and several reports have been published in recent years. is little known. In addition, malaria infection, which causes gastrointestinal symptoms, small intestinal lesions, damage to the mucosal barrier, and dramatic changes in the intestinal flora, affects not only the intestinal bacteria but also the environment in the intestinal lumen, including other factors. The involvement of multiple factors is assumed. Continuing from last year, this fiscal year, among the results obtained so far and the factors reported to affect the intestinal environment, we investigated using antibiotics. Plasmodium berghei ANKA strain (PbA)-infected C57BL/6 mice, in which the intestinal microbiota was markedly altered by ad libitum administration of antibiotics for 2 weeks, significantly induced cerebral edema and blood-brain barrier disruption. 70% to 80% of mice avoid fatality due to cerebral malaria. The effect of the intestinal flora altered by antibiotics on the immune system was investigated and it was found that the infiltration of leukocytes, including CD8+ T cells, into the brain was significantly reduced in the antibiotic-administered group. In addition, it was observed that the cerebral symptom time was clearly changed by colonizing germ-free mice with PbA-infected mice identified by bacterial flora analysis using a next-generation sequencer. Since it was suggested that intestinal bacteria may control the onset of cerebral symptoms, gnotobiotics will continued to be studied in a sterile environment and try to elucidate the mechanism of action in more detail.

Project details

Basic Science

Apr 2020 — Mar 2023

$42,677

Japan