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Avian schistosomes of the genus Trichobilharzia are the primary causative agent of cercarial dermatitis in humans but despite its worldwide occurrence, little is known of the immune mechanism of this disease (Horák et al., 2003). In collaboration with two groups at the Charles University in the Czech Republic (Drs. P. Horák and L. Kolářová), we have investigated the dermal reaction to Trichobilharzia regenti using a murine model of infection to single (1x) and multiple (4x) exposures to the parasite. We found that penetration of cercariae into the skin evoked immediate oedema, and an influx of leukocytes including neutrophils, macrophages, CD4+ lymphocytes and mast cells (Fig.1) (Kouřilová et al., 2004). A large proportion of the latter were in the process of degranulating. After 1x infection, inflammation was accompanied by the release of IL-1b, IL-6, and IL-12p40. In contrast, in 4x re-infected animals the production of histamine, IL-4 and IL-10 was dramatically elevated within 1 h of infection (Fig. 2; Kouřilová et al. 2004). Analysis of antigen-stimulated lymphocytes from the skin-draining lymph nodes revealed that cells from 1x infected mice produced a mixed Th1/Th2 cytokine response, whilst cells from 4x re-infected mice were Th2 polarised dominated by IL-4 and IL-5. Serum antibodies confirmed this polarisation with elevated levels of IgG1 and IgE after multiple infections.
Our results are the first demonstration that cercarial dermatitis, caused by bird schistosomes, is characterised by an early type I hypersensitivity reaction and a late phase of cutaneous inflammation, both associated with a polarised Th2-type acquired immune response. Infection with radio-labelled cercariae revealed that almost 90 % of larvae remained in the skin and the majority died within 8 days after infection although parasites were cleared more rapidly in 4x re-infected mice. This suggests that molecules from the skin-resident larvae are the cause of the allergic response, and is the subject of our ongoing studies.
Figure 1: Larva of Trichobilharzia regenti
(arrowed), penetrating the skin (mouse pinna) 1 hour after exposure. The
parasite is attached to the epidermis under the stratum corneum.