期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-09894-8
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资金
- German Center for Infection Research, Braunschweig, Germany [TTU 02.902_00]
- Werner Otto Stiftung, Hamburg, Germany
- Leibniz Graduate School, Leibniz Center Infection, Bernhard Nocht Institute
- Heinrich Pette Institute, Hamburg, Germany
- Stiftung Industrieforschung, Essen, Germany
- Japan Society for the Promotion of Science (JSPS) [JP26282211, JP26102732, JP16H01162]
- NEXT Program from the JSPS [LR025]
- Mizutani Foundation for Glycoscience, Japan
- NEXT Program from the CSTP [LR025]
- Grants-in-Aid for Scientific Research [15H05836, 17H05800, 16H01014, 16H01162, 17F17415, 17H02207, 16H01885, 16F16339] Funding Source: KAKEN
Intracellular pathogens belonging to the genus Leishmania have developed effective strategies that enable them to survive within host immune cells. Immunostimulatory compounds that counteract such immunological escape mechanisms represent promising treatment options for diseases. Here, we demonstrate that a lipopeptidephosphoglycan (LPPG) isolated from the membrane of a protozoan parasite, Entamoeba histolytica (Eh), shows considerable immunostimulatory effects targeted against Leishmania (L.) major, a representative species responsible for cutaneous leishmaniasis (CL). Treatment led to a marked reduction in the number of intracellular Leishmania parasites in vitro, and ameliorated CL in a mouse model. We next designed and synthesized analogs of the phosphatidylinositol anchors harbored by EhLPPG; two of these analogs reproduced the anti-leishmanial activity of the native compound by inducing production of pro-inflammatory cytokines. The use of such compounds, either alone or as a supportive option, might improve the currently unsatisfactory treatment of CL and other diseases caused by pathogen-manipulated immune responses.
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