The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production.
In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (MΦ) from MR(-/-) mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR(-/-) mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFNγ but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFNγ.
Centre for Immunology and Infection, Department of Biology, The University of York, York YO10 5DD, UK.
Ross A
RA
Paveley
Sarah A
SA
Aynsley
Joseph D
JD
Turner
Claire D
CD
Bourke
Stephen J
SJ
Jenkins
Peter C
PC
Cook
Luisa
L
Martinez-Pomares
Adrian P
AP
Mountford
D000818:Animals; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology*; D012550:Schistosoma mansoni / Q000254:growth & development / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D051192:Receptors, Pattern Recognition; D007371:Interferon-gamma