Trichobilharzia regenti: Өмірі мен таралуы

Species of fluke
Speciesbox
|image=Trichobilharzia. regenti. cercaria. DIC. png
|image caption=Trichobilharzia regenti, cercaria
|taxon=Trichobilharzia regenti
|authority=Horák, Kolářová & Dvořák, 1998 The species was originally described in 1998 in the Czech Republic and afterwards it was detected also in other European countries, e. g. Denmark, Germany, France, Iceland, Poland, Switzerland, or Russia, and even in Iran. For its unique neurotropic behaviour in vertebrate hosts, the host parasite interactions are extensively studied in terms of molecular biology, biochemistry and immunology.

The life cycle of T. regenti is analogous to that of human schistosomes. Adult flukes mate in a nasal mucosa of anatid birds (e. g. Anas platyrhynchos, Spatula clypeata or Cairina moschata) and produce eggs with miracidia which hatch directly in the host tissue and leak outside when the bird is drinking/feeding. In the snail, the miracidia develop into a primary sporocyst in which secondary sporocysts are formed and give rise to cercariae later on. Cercariae, infective larvae, exit the snail and penetrate the skin of an avian host. After penetration of the host's skin, they shed the immunogenic surface glycocalyx and transform to schistosomula (subadult stage, sg. schistosomulum). Schistosomula then look for peripheral nerves to use them to get to the spinal cord. Through it they continue their migration to the brain and, finally, the nasal tissue in a bill. Here, they mature, copulate and lay eggs while causing pathology (inflammatory infiltration, haemorrhages). If mammals are infected by cercariae (instead of birds), the parasites die in the skin being entrapped by immune response. The clinical manifestation of such infection is known as a neglected allergic disease called cercarial dermatitis (or swimmer's itch). In mice, especially in immunodeficient ones, migration of the parasite to the spinal cord was observed. A complete life cycle of T. regenti can be maintained under laboratory conditions using Radix lagotis and the Domestic duck (Anas platyrhynchos f. domestica) as intermediate and definitive hosts, respectively. Experiments with laboratory prepared recombinant form of the cysteine peptidase cathepsin B2 of T. regenti (TrCB2) confirmed its ability to cleave skin proteins (collagen, keratin and elastin). After penetration the skin, cercariae transform to schistosomula and start a migration through the host's body. They avoid penetration into blood capillaries and rather prefer entering peripheral nerves in host's limbs. Schistosomula are found in peripheral nerves of ducks and mice as soon as 1.5 and 1 day post infection (DPI), respectively. Based on recent observation by 3D imaging techniques (ultramicroscopy and micro CT), schistosomula appear to migrate preferably through the white matter of the spinal cord in both birds and mammals. The next course of the infection differs in final and accidental hosts. In ducks, schistosomula are observed in synsacral segments of a spinal cord 3 DPI and 7–8 days later (10–11 DPI) they reach the brain. In their final localisation (the nasal tissue), they occur 13–14 DPI and laying eggs starts 15 DPI. Nonetheless, the nervous tissue ingestion has likely only a minor pathogenic effect on the host central nervous tissue. Recently, massive downregulation of neurophysiological pathways was suggested to be responsible for the motor dysfunction detected also in properly examined immunocompetent mice. In the CNS, eosinophils and heterophils surround the parasite but do not prevent its migration towards the final localisation in the nasal mucosa.

The infection manifests as early type I hypersensitivity reaction and a late phase cutaneous inflammation. Cellular immune response is represented by production of pro inflammatory (IL 1β, IL 6 and IL 12p40) and anti inflammatory (IL 10) cytokines in a skin of mice infected for the first time. On the contrary, anti inflammatory IL 4 and IL 10 dominate in mice infected repeatedly which also secrete large amounts of histamine from mast cells. Lymphocytes from their skin draining lymph nodes produce IL 4 and IL 5 after stimulation with parasite antigens which shows Th2 polarization of host immune response. IgM antibody response targets mainly carbohydrate epitopes of parasite molecules. Increased production of antigen specific IgG1 and total IgE, but slight decrease in antigen specific IgG2b corroborate Th2 immune polarization in repeatedly infected individuals.

Clinical manifestation of human immune response to T. regenti infection is known as cercarial dermatitis (aka swimmer's itch). Majority of humans (82% of adults, 57% of children) who have experienced cercarial dermatitis (caused by undetermined species of bird schistosome) have increased levels of T. regenti antigen specific IgG, but not IgE. Cercarial homogenate and excretory secretory products of T. regenti induce basophils from humans without a history of cercarial dermatitis to degranulate and release IL 4.