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

Date Published: January 30, 2019

Publisher: Public Library of Science

Author(s): Christian Hidalgo, Caroll Stoore, Karen Strull, Carmen Franco, Felipe Corrêa, Mauricio Jiménez, Marcela Hernández, Karina Lorenzatto, Henrique B. Ferreira, Norbel Galanti, Rodolfo Paredes, Massimiliano Galdiero.


Cystic 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.

We 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.

This 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.

Partial Text

Cystic echinococcosis (CE) is a major zoonotic disease caused by infection with the metacestode stage (hydatid cyst) of the flatworm Echinococcus granulosus. It has a worldwide distribution with an estimated 4 million people infected and another 40 million at risk [1]. High parasite prevalence is found in Eurasia, Africa, Australia and South America. CE affects more severely South American countries characterized by extensive grazing livestock farming including Argentina, Brazil, Chile, Peru, and Uruguay [2]. The life cycle of this parasite includes two mammal hosts. The definitive hosts are dogs and other canids; while ungulates and other mammals act as intermediate hosts [3] such as sheep, goats, cattle, pigs, buffaloes, horses and camels [4]. The most common infection sites in cattle are the liver and lungs [5–7]. Within these viscera, a unilocular cyst forms, that will grow gradually from 1 to 5 cm a year [8]. The hydatid cyst is circumscribed by a layer generated by the intermediate host in response to the parasite, named adventitial layer, which mainly consists of epithelial cells and connective tissue [9]. The adventitial layer can have variable thickness and may present some focal fibrosis as result of host immune response that considers the cyst a foreign body [10]. The lumen of the hydatid cyst is filled with the so called hydatid fluid and is surrounded by two layers of parasite tissue; the innermost cellular layer is called germinal layer and is intimately attached to an acellular layer called laminated layer, the latter is in close contact with the adventitial layer. The germinal layer is composed by embryonic cells whose function is to elaborate the different elements of hydatid cysts [10]. These embryonic cells differentiate into buds that finally generate protoscoleces (PSC), the infectious parasite form for the definite host [8]. The laminated layer is generated by the germinal layer and is described as a specialized extracellular matrix that is found only in the genus Echinococcus [11]. Macroscopically, it is seen as a whitish membrane, formed by various layers of mucopolysaccharides and keratin, evolutionarily adapted to maintain the physical integrity of metacestodes and to protect the cells of the germinal layer from host immunity [12]. In the intermediate host, it is possible to find two different types of hydatid cysts: fertile hydatid cysts, in which PSC are attached to the germinal layer and free into the hydatid fluid. Fertile hydatid cyst PSC viability, that is, the percentage of live PSC, varies between 100% and 2,8% [13–17]. Contrarily, infertile hydatid cysts (also called sterile hydatid cysts [18–23]), have no PSC neither attached to the germinal layer nor floating free in the hydatid fluid, and thus are unable to continue with the parasite life cycle. The reason behind why infertile hydatid cysts are unable to produce PSC remains unclear [24]. In many geographical areas, including Chile [25], cattle has been associated with low fertile hydatid cysts counts (<30%) in both Echinococcus granulosus sensu lato [26–29] and Echinococcus granulosus sensu stricto [6, 22], so it is a suitable model to study cyst infertility mechanisms. Our research team, so far has been working in understanding the causes of infertile hydatid cyst in cattle, identifying both higher apoptosis levels in germinal layer of infertile cysts [24] and different immunoglobulin profiles [30]. Possible relations of the laminated and adventitial layers with fertility or infertility, however, have never been addressed. In this work, we present a systematic comparative study of both the laminated and adventitial layer in fertile and infertile hydatid cysts obtained from naturally infected cattle. Protoscolex viability of fertile hydatid cysts is determined; morphohistological characteristics of hydatid cysts are described and compared, demonstrating the infiltration of host immune cells inside infertile hydatid cysts, and providing evidences of their effect on and contribution to cyst integrity and fertility. Echinococcus granulosus infection of the intermediate host elicits a granulomatous tissue reaction; characterized by the accumulation of cells of monocytic origin and are thought to be directed both at walling off and at eliminating the persistent foreign body. The hallmarks of granulomatous reactions are special types of activated macrophages called epithelioid cells and multinucleated giant cells [32].   Source:


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