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

• Published in: International journal for parasitology Vol. 41; no. 13; pp. 1335 - 1345
• Main Authors: Paveley, Ross A., Aynsley, Sarah A., Turner, Joseph D., Bourke, Claire D., Jenkins, Stephen J., Cook, Peter C., Martinez-Pomares, Luisa, Mountford, Adrian P.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-11-2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Helminth glycans; Humans; Immune regulation; Interferon-gamma - genetics; Interferon-gamma - immunology; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Life cycle. Host-agent relationship. Pathogenesis; Male; Mannose Receptor; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - immunology; Mice; Mice, Inbred C57BL; Protozoa; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Pattern Recognition - genetics; Receptors, Pattern Recognition - immunology; Schistosoma mansoni; Schistosoma mansoni - growth & development; Schistosoma mansoni - physiology; Schistosomiasis mansoni - genetics; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - parasitology; Th2 Cells - immunology; Schistosoma mansoni; Immune regulation; Helminth glycans; Mannose Receptor; Plathelmintha; Parasite; Mannose; Pattern recognition; Trematoda; Glycan; Helmintha; Invertebrata; Detection
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2011.08.005

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► Excretory/secretory (E/S) material from schistosome cercariae contains an abundance of glycans. ► Larval E/S has high binding specificity for the Mannose Receptor (MR). ► MR
+ cell lines internalised greater levels of fluorescent labelled larval E/S. ► Macrophages from MR deficient mice take up less larval E/S but are more active. ► In the absence of MR, CD4
+ T cells secreted increased IFNγ but reduced IL-4.
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.