The shiitake mushroom-derived immuno-stimulant lentinan protects against murine malaria blood-stage infection by evoking adaptive immune-responses

Int Immunopharmacol. 2009 Apr;9(4):455-62. doi: 10.1016/j.intimp.2009.01.010. Epub 2009 Feb 2.

Abstract

Lentinan, a (1-3)-beta glucan from Lentinus edodes, is an effective immunostimulatory drug. We tested the effects of lentinan during blood-stage infection by Plasmodium yoelii 17XL (P.y17XL). Pre-treatment of mice with lentinan significantly decreased the parasitemia and increased their survival after infection. Enhanced IL-12, IFN-gamma and NO production induced by lentinan in spleen cells of infected mice revealed that the Th1 immune response was stimulated against malaria infection. In vitro and in vivo, lentinan can result in enhanced expression of MHC II, CD80/CD86, and Toll-like receptors (TLR2/TLR4), and increased production of IL-12 in spleen dendritic cells (DCs) co-cultured with parasitized red blood cells (pRBCs). Moreover, both the number of CD4(+)CD25(+) regulatory T cells (Tregs) and the levels of IL-10 secreted by Tregs were reduced by pre-treatment with lentinan in the spleen of malaria-infected mice. Meanwhile, apoptosis of CD4(+) T cell in spleens of mice pretreated with lentinan was significantly reduced. In summary, lentinan can induce protective Th1 immune responses to control the proliferation of malaria parasites during the blood-stage of P.y17XL infection by stimulating maturation of DCs to inhibit negative regulation of the Th1 immune response by Tregs. Taken together, our findings suggest that lentinan has prophylactic potential for the treatment of malaria.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / parasitology
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Interferon-gamma / agonists
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-12 / agonists
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Lentinan / administration & dosage
  • Lentinan / therapeutic use*
  • Malaria / complications
  • Malaria / drug therapy*
  • Malaria / immunology
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / agonists
  • Nitric Oxide / immunology
  • Nitric Oxide / metabolism
  • Parasitemia / etiology
  • Parasitemia / immunology
  • Parasitemia / prevention & control*
  • Plasmodium yoelii*
  • Shiitake Mushrooms / chemistry
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / parasitology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / parasitology
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Adjuvants, Immunologic
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Histocompatibility Antigens Class II
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Interleukin-12
  • Nitric Oxide
  • Lentinan
  • Interferon-gamma