Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17+ γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets.

• MeSH
• Dendritic Cells immunology   MeSH
• Interleukin-33 * metabolism   immunology   MeSH
• Skin immunology   parasitology   MeSH
• Humans MeSH
• Macrophages immunology   metabolism   MeSH
• Myeloid Cells immunology   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Neurons immunology   metabolism   MeSH
• Pruritus immunology   MeSH
• Receptors, G-Protein-Coupled * metabolism   immunology   genetics   MeSH
• Schistosoma mansoni * immunology   MeSH
• Schistosomiasis mansoni * immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Il33 protein, mouse MeSH Browser
• Interleukin-33 * MeSH
• Receptors, G-Protein-Coupled * MeSH

Helminth neuroinfections represent serious medical conditions, but the diversity of the host-parasite interplay within the nervous tissue often remains poorly understood, partially due to the lack of laboratory models. Here, we investigated the neuroinvasion of the mouse spinal cord by Trichobilharzia regenti (Schistosomatidae). Active migration of T. regenti schistosomula through the mouse spinal cord induced motor deficits in hindlimbs but did not affect the general locomotion or working memory. Histological examination of the infected spinal cord revealed eosinophilic meningomyelitis with eosinophil-rich infiltrates entrapping the schistosomula. Flow cytometry and transcriptomic analysis of the spinal cord confirmed massive activation of the host immune response. Of note, we recorded striking upregulation of the major histocompatibility complex II pathway and M2-associated markers, such as arginase or chitinase-like 3. Arginase also dominated the proteins found in the microdissected tissue from the close vicinity of the migrating schistosomula, which unselectively fed on the host nervous tissue. Next, we evaluated the pathological sequelae of T. regenti neuroinvasion. While no demyelination or blood-brain barrier alterations were noticed, our transcriptomic data revealed a remarkable disruption of neurophysiological functions not yet recorded in helminth neuroinfections. We also detected DNA fragmentation at the host-schistosomulum interface, but schistosomula antigens did not affect the viability of neurons and glial cells in vitro. Collectively, altered locomotion, significant disruption of neurophysiological functions, and strong M2 polarization were the most prominent features of T. regenti neuroinvasion, making it a promising candidate for further neuroinfection research. Indeed, understanding the diversity of pathogen-related neuroinflammatory processes is a prerequisite for developing better protective measures, treatment strategies, and diagnostic tools.

• MeSH
• Arginase metabolism   MeSH
• Biomarkers metabolism   MeSH
• Chemokines metabolism   MeSH
• Eosinophils metabolism   MeSH
• Major Histocompatibility Complex MeSH
• Immunity MeSH
• Trematode Infections immunology   metabolism   pathology   MeSH
• Host-Parasite Interactions MeSH
• Spinal Cord parasitology   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neuroglia parasitology   MeSH
• Neurons parasitology   MeSH
• Schistosomatidae immunology   MeSH
• Gene Expression Profiling MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Arginase MeSH
• Biomarkers MeSH
• Chemokines MeSH

Cercarial dermatitis (CD) is an allergic skin disease that rises in consequence of infection by invasive stages (cercariae) of trematodes of the family Schistosomatidae. CD has been considered a re-emerging disease, human cases have been reported from all continents, and tourism-threatening outbreaks occur even in frequented recreational areas. Although the symptoms of CD are generally known, the data on immune response in human patients are sporadic and incomprehensive. In the present study, we attempted to correlate the symptoms, personal history, and time course of CD in human patients with differential cell counts, dynamics of selected cytokines, and dynamics and quality of antibody response. By a systematic follow-up, we obtained a uniquely complex dataset from ten persons accidentally and concurrently infected by the same parasite species in the same locality. The onset of CD was significantly faster, and the symptoms were heavier in participants with a history of CD if compared to naive ones, who, however, also developed some of the symptoms. The repeatedly infected persons had elevated proportion of eosinophils 1 week post exposure (p.e.) and a stronger specific IgG but not IgM response, whereas specific IgE response was not observed. Increased serum levels of IL-4 occurred 1 and 3 week(s) p.e. in all participants. There was high variability in individual immunoblot patterns of IgG response, and no antigen with a universal diagnostic potential was confirmed. The presented analyses suggested that a complex approach can improve the accuracy of the diagnosis of CD, but component data should be interpreted carefully.

• Keywords
• Allergy, Diagnosis, Immunity, Schistosome, Skin, Trichobilharzia,
• MeSH
• Dermatitis immunology   parasitology   MeSH
• Adult MeSH
• Disease Outbreaks MeSH
• Immunoglobulin E blood   MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Trematode Infections diagnosis   immunology   parasitology   MeSH
• Interleukin-4 blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Antibodies, Protozoan blood   MeSH
• Surveys and Questionnaires MeSH
• Ponds parasitology   MeSH
• Schistosomatidae immunology   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• IL4 protein, human MeSH Browser
• Immunoglobulin E MeSH
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Interleukin-4 MeSH
• Antibodies, Protozoan MeSH

Nasal bird schistosomes can cause bilharziosis in birds and have the potential to cause swimmer's itch in humans. We determined the prevalence of bird schistosomes in 106 mallards (Anas plathyrhynchos) from 11 water sources in Germany from 2014. Dissections were performed focusing on parasitic infections of the neural system. Infections with Trichobilharzia regenti (Horák et al. 1998) were found in 21% of the birds (n = 22), whereas Bilharziella polonica (Kowalewski 1895) were found between the brain membranes (meninges) and the brain, in the spinal cord or in the intestine of 12% of the mallards (n = 13). No significant influence of sex, age, and body condition between infected and non-infected animals was observed. Our study provides the first description of B. polonica from the neural system of birds and provides an epidemiological understanding of a parasite of human health concern.

• Keywords
• Bilharziella polonica, Bird schistosomes, Mallard, Trichobilharzia regenti,
• MeSH
• Animals, Wild parasitology   MeSH
• Trematode Infections parasitology   veterinary   MeSH
• Ducks parasitology   MeSH
• Humans MeSH
• Bird Diseases parasitology   MeSH
• Nervous System parasitology   MeSH
• Schistosoma genetics   isolation & purification   physiology   MeSH
• Schistosomatidae genetics   isolation & purification   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Germany MeSH

BACKGROUND: The nasal avian schistosome Trichobilharzia regenti spends part of its intravertebrate period of life within the central nervous system. Migration of the parasites can be accompanied by neuromotor disorders or paralysis in natural definitive hosts (ducks) and even in laboratory mammals. Cercariae are also able to penetrate human skin and induce cercarial dermatitis. While the cellular and antibody responses against cercariae and migrating schistosomula have been investigated in mice, little is known about immune reactions in birds. This study first describes the dynamics of antibody response in infected ducks and identifies frequently recognized antigens that may serve as diagnostic markers of infection by T. regenti. METHODS: Groups of 35 domestic ducks and 10 mallards were exposed to different doses of T. regenti cercariae. Sera were collected at predefined time intervals and tested by ELISA for the presence of specific anti-cercarial IgY and IgM. Antigens recognized by the antibodies were identified on Western blots of cercariae and schistosomula. The applicability in immunodiagnostics was statistically evaluated by expression of specificity and sensitivity values for individual antigens. RESULTS: In ELISA, the levels of anti-cercarial IgM peaked on day 15 pi. Increased production of IgY associated with the later phases of infection was observed in most individuals around 20 dpi and culminated 30 dpi. The time course of antibody response did not differ among experimental groups, variations were only observed in the levels of specific IgY which depended rather on the age of ducks at the time of infection than on the infectious dose. On Western blots, 40 cercarial and 7 schistosomular antigens were recognized by IgY from infected ducks. Among them, 4 cercarial antigens of 50, 47, 32 and 19 kDa provided the most sensitive and specific reactions. CONCLUSIONS: Antigens of cercariae and schistosomula elicited distinct antibody response in ducks, which correlated positively with the age of animals at the time of infection. Several antigens originating in cercariae and fewer in schistosomula were recognized by IgY with diverse sensitivity and specificity; only a few seemed to be common to both stages. Four of them were considered as the most promising candidates for immunodiagnostics.

• MeSH
• Antigens, Helminth immunology   MeSH
• Immunoglobulin M blood   MeSH
• Immunoglobulins blood   MeSH
• Trematode Infections blood   immunology   parasitology   veterinary   MeSH
• Ducks * MeSH
• Bird Diseases blood   immunology   parasitology   MeSH
• Antibodies, Helminth blood   MeSH
• Schistosomatidae * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antigens, Helminth MeSH
• IgY MeSH Browser
• Immunoglobulin M MeSH
• Immunoglobulins MeSH
• Antibodies, Helminth MeSH

Cercarial dermatitis (swimmer's itch) is a condition caused by infective larvae (cercariae) of a species-rich group of mammalian and avian schistosomes. Over the last decade, it has been reported in areas that previously had few or no cases of dermatitis and is thus considered an emerging disease. It is obvious that avian schistosomes are responsible for the majority of reported dermatitis outbreaks around the world, and thus they are the primary focus of this review. Although they infect humans, they do not mature and usually die in the skin. Experimental infections of avian schistosomes in mice show that in previously exposed hosts, there is a strong skin immune reaction that kills the schistosome. However, penetration of larvae into naive mice can result in temporary migration from the skin. This is of particular interest because the worms are able to migrate to different organs, for example, the lungs in the case of visceral schistosomes and the central nervous system in the case of nasal schistosomes. The risk of such migration and accompanying disorders needs to be clarified for humans and animals of interest (e.g., dogs). Herein we compiled the most comprehensive review of the diversity, immunology, and epidemiology of avian schistosomes causing cercarial dermatitis.

• MeSH
• Biodiversity MeSH
• Disease Outbreaks MeSH
• Host Specificity MeSH
• Humans MeSH
• Bird Diseases parasitology   transmission   MeSH
• Skin Diseases, Parasitic epidemiology   immunology   parasitology   prevention & control   MeSH
• Birds MeSH
• Schistosomiasis epidemiology   immunology   parasitology   prevention & control   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Cercarial dermatitis (swimmer's itch) is a common non-communicable water-borne disease. It is caused by penetration of the skin by larvae (cercariae) of schistosomatid flukes and develops as a maculopapular skin eruption after repeated contacts with the parasites. The number of outbreaks of the disease is increasing, and cercarial dermatitis can therefore be considered as an emerging problem. Swimmer's itch is mostly associated with larvae of the bird schistosomes of Trichobilharzia spp. Recent results have shown that mammalian infections (including man) manifest themselves as an allergic reaction which is able to trap and eliminate parasites in the skin. Studies on mammals experimentally infected by bird schistosome cercariae revealed, however, that during primary infection, parasites are able to escape from the skin to the lungs or central nervous system. This review covers basic information on detection of the infectious agents in the field and the clinical course of the disease, including other pathologies which may develop after infection by cercariae, and diagnosis of the disease.

• MeSH
• Central Nervous System microbiology   MeSH
• Cercaria immunology   MeSH
• Dermatitis diagnosis   immunology   parasitology   MeSH
• Skin microbiology   pathology   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Swimming MeSH
• Lung microbiology   MeSH
• Schistosoma MeSH
• Schistosomiasis complications   diagnosis   immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Bird schistosomes, besides being responsible for bird schistosomiasis, are known as causative agents of cercarial dermatitis. Cercarial dermatitis develops after repeated contact with cercariae, mainly of the genus Trichobilharzia, and was described as a type I, immediate hypersensitivity response, followed by a late phase reaction. The immune response is Th2 polarized. Primary infection leads to an inflammatory reaction that is insufficient to eliminate the schistosomes and schistosomula may continue its migration through the body of avian as well as mammalian hosts. However, reinfections of experimental mice revealed an immune reaction leading to destruction of the majority of schistosomula in the skin. Infection with the nasal schistosome Trichobilharzia regenti probably represents a higher health risk than infections with visceral schistosomes. After the skin penetration by the cercariae, parasites migrate via the peripheral nerves, spinal cord to the brain, and terminate their life cycle in the nasal mucosa of waterfowl where they lay eggs. T. regenti can also get over skin barrier and migrate to CNS of experimental mice. During heavy infections, neuroinfections of both birds and mammals lead to the development of a cellular immune response and axonal damage in the vicinity of the schistosomulum. Such infections are manifest by neuromotor disorders.

• Publication type
• Journal Article MeSH