The shiitake mushroom-derived immuno-stimulant lentinan protects against murine malaria blood-stage infection by evoking adaptive immune-responses.
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.
Zhou
Lian-di
LD
Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Zhang
Qi-hui
QH
Zhang
Ying
Y
Liu
Jun
J
Cao
Ya-ming
YM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D007912:Lentinan / Q000008:administration & dosage / Q000627:therapeutic use*; D008288:Malaria / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D018512:Parasitemia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D010967:Plasmodium yoelii; D020942:Shiitake Mushrooms / Q000737:chemistry; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D009569:Nitric Oxide; D007912:Lentinan; D007371:Interferon-gamma