Avian schistosomes 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. Using a murine model, hosts were exposed to primary (1×) and multiple (4×) infections of Trichobilharzia regenti via the pinna. Penetration of larvae into the skin evoked immediate edema, thickening of the exposure site, and an influx of leukocytes, including neutrophils, macrophages, CD4+ lymphocytes, and mast cells. A large proportion of the latter were in the process of degranulating. After 1× infection, inflammation was accompanied by the release of IL-1β, IL-6, and IL-12p40. In contrast, in 4× reinfected animals the production of histamine, IL-4, and IL-10 was dramatically elevated within 1 h of infection. Analysis of Ag-stimulated lymphocytes from the skin-draining lymph nodes revealed that cells from 1× infected mice produced a mixed Th1/Th2 cytokine response, including abundant IFN-γ, whereas cells from 4× reinfected mice were Th2 polarized, dominated by IL-4 and IL-5. Serum Abs confirmed this polarization, with elevated levels of IgG1 and IgE after multiple infections. Infection with radiolabeled 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 4× reinfected mice. Our results are the first demonstration that cercarial dermatitis, caused by bird schistosomes, is characterized by an early type I hypersensitivity reaction and a late phase of cutaneous inflammation, both associated with a polarized Th2-type acquired immune response.

Cercariae of the nasal bird schistosome Trichobilharzia regenti are able to penetrate into mammalian skin and migrate to the mouse central nervous system (CNS) causing tissue injury in certain cases. Our study shows that the severity of T. regenti pathologies in the CNS closely depends on the host immune status. During the primary infection of immunocompetent mice, the parasites evoked an acute inflammatory reaction in the skin and the CNS involving focal oedema and cellular infiltration of the tissue. Challenge infections resulted in the development of extensive inflammatory foci in the host skin which precluded the subsequent migration of the schistosomula to the CNS. On the other hand, during primary as well as challenge infections of immunodeficient mice (SCID), no significant immune response against the parasites was detected in any of the host organs examined; however, in contrast to immunocompetent mice, the infections were frequently manifested by severe leg paralysis.

Cercariae of bird schistosomes (genus Trichobilharzia) are able to penetrate the skin of mammals (noncompatible hosts), including humans, and cause a Th2-associated inflammatory cutaneous reaction termed cercarial dermatitis. The present study measured the antibody reactivity and antigen specificity of sera obtained after experimental infection of mice and natural infection of humans. Sera from mice re-infected with T. regenti showed a bias towards the development of antigen-specific IgM and IgG1 antibodies and elevated levels of total serum IgE, indicative of a Th2 polarized immune response. We also demonstrate that cercariae are a source of antigens triggering IL-4 release from basophils collected from healthy human volunteers. Analysis of sera from patients with a history of cercarial dermatitis revealed elevated levels of cercarial-specific IgG, particularly for samples collected from adults (> 14 years old) comparedwith children (8–14 years old), although elevated levels of antigen-specific IgE were not detected. In terms of antigen recognition, IgG and IgE antibodies in the sera of both mice and humans preferentially bound an antigen of 34 kDa. The 34 kDa molecule was present in both homogenate of cercariae, as well as cercarial excretory/secretory products, and we speculate it may represent a major immunogen initiating the Th2-immune response associated with cercarial dermatitis.

Schistosome cercariae are able to penetrate into the skin of various vertebrate hosts. However, in contrast to the compatible host, the infection of incompatible hosts results in the death of parasites at various intervals post-infection. In order to compare the immune responses in both types of host infected with Trichobilharzia regenti, Trichobilharzia szidatior Schistosoma mansoni, antibody responses against various T. regenti, T. szidatiand S. mansonischistosome developmental stages were studied. Indirect immunofluorescence tests (IFAT) demonstrated no species-specific reactivity of human, mouse or duck immune sera with cercarial surfaces. Study of the cercarial glands also gave no significant results. However, differences were found in schistosomular and adult antigens: only the sera of compatible hosts recognised schistosomular and adult gut associated antigens in homologous as well as heterologous systems. Based on the presented data, our study supports the use of IFAT for the serological differentiation of schistosomiasis and cercarial dermatitis caused by bird schistosomes.