New insights of the local immune response against both fertile and infertile hydatid cysts

Abstract

BackgroundCystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role.Methodology/Principal fidingsWe collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer.Conclusions/SignificanceThis is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst.Author SummaryCystic echinococcosis is caused by the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, mainly liver and lungs of herbivores such as cows and sheep as well as human beings, the parasite grows as a unilocular cyst known as hydatid cyst. These cysts develop in their inner chamber a structure known as protoscolex, when consumed by the definitive host (e.g. dogs), it grows into a worm that resides in the small intestine and produces eggs that contaminate the environment. In cattle, most hydatid cysts are unable to produce protoscoleces, and thus are termed infertile hydatid cysts. The molecular mechanisms that explain the causes of hydatid cyst infertility remain unknown. We routinely collected cattle hydatid cysts from both liver and lugs and processed them for histological analysis. We found that there is a subset of fertile hydatid cysts that have low protoscolex viability and high immune infiltration surrounding the cyst. All infertile cysts have high immune infiltration, and many of them show disruption of the laminated layer and immune cells of host origin inside the cyst. This is the first report that shows that the cyst can be infiltrated by the host immune system.

Cattle co-infection of Echinococcus granulosus and Fasciola hepatica results in a different systemic cytokine profile than single parasite infection

“…Two kinds of Echinococcal cysts are found In naturally infected intermediate hosts; (1) fertile cysts, in which protoscoleces are attached to the germinal layer or free into the hydatid fluid; and (2) infertile cysts, where protoscoleces are absent and the parasite life cycle ends [ 24 ]. The reason why these two type of cysts exist is unclear [ 25 ].…”

“…The reason why these two type of cysts exist is unclear [ 25 ]. The host immune response is likely to participate in generating infertile Echinococcus cysts [ 24 ]. However, the parasite antigen that drives this immune response remains unknown.…”

Fasciola hepatica coinfection modifies the morphological and immunological features of Echinococcus granulosus cysts in cattle

“…EC fertility is associated with the intensity of the inflammatory reaction in the adventitial layer [40], and Fasciola hepatica modifies the cattle systemic immune response [35]. We hypothesized that adventitial layer characteristics are associated with coinfection status.…”

“…Lung ECs frequently show an absence of calcification, necrosis under the laminated layer, and palisading macrophages of the adventitial layer. These findings suggest a positive environment for EC growth, as the presence of these histological features is the hallmark of the granulomatous reaction associated with EC infertility [40]. Fasciola hepatica modulates host macrophages, stimulates fibrosis, and inhibits TLR3 and TLR4 activity (both of which are T H 1-associated receptors and thus are detrimental for EC survival) [46].…”

“…Samples were processed as previously described [40]. Briefly, fixed samples were cut, oriented transversally and inserted into biopsy cassettes.…”