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.