4.8 Article

Mannose inhibits Plasmodium parasite growth and cerebral malaria development via regulation of host immune responses

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.859228

Keywords

D-mannose; parasitemia; cerebral malaria; macrophage; T cell

Categories

Funding

  1. National Natural Science Foundation of China [32070701, 32200976]
  2. Tianjin Medical University [115004/000012, 11601502/DW0114]
  3. Science & Technology Development Fund of Tianjin Education Commission for Higher Education [2018KJ085]
  4. National Laboratory of Biomacromolecules [2020kf11]

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D-mannose affects tumor growth and immune cell function through interference with glycolysis and induction of oxidative stress. In a mouse model of Plasmodium berghei infection, D-mannose reduces parasitemia and increases splenic macrophages. It also decreases the occurrence of cerebral malaria in a rodent model and reduces activation of T cells in the peripheral blood and brain.
D-mannose can be transported into a variety of cells via glucose transporter (GLUT), and supraphysiological levels of D-mannose impairs tumor growth and modulates immune cell function through mechanisms such as interference with glycolysis and induction of oxidative stress. Blood-stage Plasmodium mainly depends on glycolysis for energy supply and pathological immune response plays a vital role in cerebral malaria. However, it is not clear whether mannose affects malaria blood-stage infection. Here, we fed D-mannose to Plasmodium berghei-infected mice and found weight loss and reduced parasitemia without apparent side effects. Compromised parasitemia in C57BL/6 mice was accompanied by an increase in splenic macrophages compared to an untreated group. When mannose was applied to a rodent experimental cerebral malaria (ECM) model, the incidence of ECM decreased. Expression of activation marker CD69 on T cells in peripheral blood and the brain were reduced, and cerebral migration of activated T cells was prevented by decreased expression of CXCR3. These findings suggest that mannose inhibits Plasmodium infection by regulating multiple host immune responses and could serve as a potential strategy for facilitating malaria treatment.

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