Echinococcus multilocularis: relationship between susceptibility/ resistance and liver fibrogenesis in experimental mice

Abstract

To analyze collagen and other matrix protein deposits in experimental alveolar echinococcosis as well as the expression of lysyl oxidase, the enzyme that initiates the first steps in the pyridinoline cross-linking of collagen, and to establish a relationship between resistance/susceptibility to Echinococcus multilocularis larval growth and fibrogenesis, we compared AKR/J mice (susceptible to E. multilocularis infection) with NMRI mice (resistant hosts) in this study. Collagen deposits in the lesions were evaluated using a colorimetric method; the nature of matrix proteins involved in the periparasitic fibrosis and lysyl oxidase expression were assessed using immunostaining on tissue sections. The results obtained in this sequential study confirm that fibrogenesis is an important aspect of the host immune reaction against parasitic development and that both the extent and the course of matrix protein deposition differ in the liver of susceptible and resistant mice, respectively. The long-lasting expression of alpha-actin and lysyl oxidase by host cells in NMRI mice suggests that in this resistant strain, fibrosis was not only more developed but also more highly cross-linked and, thus, less sensitive to collagenases than in susceptible mice. A very strong expression of lysyl oxidase by parasitic cells was observed in both strains of mice; the observation that E. multilocularis itself has a role in lysyl oxidase cross-linking of host collagens can be hypothesized and would be a new example of parasite-host interplay.

Cysticercus fasciolaris infection in wild rats (Rattus norvegicus) in Korea and formation of cysts by remodeling of collagen fibers

“…28 To protect the liver parenchyma from the larva, the infected livers then form a capsule surrounding the larva, composed of infiltrated inflammatory cells and collagen fibers secreted by HSCs and/or myofibroblasts. 15,28 As the larva develops, it becomes fully encapsulated, and the number of inflammatory cells decreases. Thereafter, the larvae are judged by the host to no longer be a severe irritant to the liver and the immune response abates.…”

“…This sequence of events resembles the process by which granulation tissue forms following Mesocestoides vogae and Echinococcus multilocularis infection in the liver. 6,15,16 In addition, collagen type I fibers are known to be a stronger form of the structural protein than collagen type III. 1 Therefore, as the larva develops, the cyst wall, composed of collagen networks, gradually becomes tougher.…”

Contribution of myeloid cell subsets to liver fibrosis in parasite infection

“…However, in the case of E multilocularis, the embedding of parasitic vesicles in heavily crosslinked collagens also 192 A Beschin et al leads to metacestode death. Accordingly, it has been demonstrated that mouse strains with higher fibrogenic activity are more resistant to the disease [147,148]. Of note, the periparasitic fibrotic lesions are very dense and cannot rupture.…”

First Case of <i>Echinococcus multilocularis</i> Infection in a Zoo-Housed Flying Squirrel (<i>Pteromys volans orii</i>)

“…multilocularis lesion is characterized by a granulomatous host reaction that includes infiltration of cells including lymphocytes, epithelioid cells and multinucleated giant cells and fibrosis [4,13]. These periparasitic reactions surrounding the metacestode vesicles were not markedly different in the small mammal intermediate hosts including the experimental murine model and our flying squirrel case [2,8].…”

“…The periparasitic granuloma and fibrosis protect the host against the parasite's growth. In experimental murine model and human cases [4,13], the correlation between resistance and development of fibrosis suggests that fibrogenesis is an important component of the immunologically mediated effector mechanisms that limit larval growth. Since thin fibrosis in the periphery of the metacestode expanding growth does not seem to inhibit the infiltrative growth in this case, the flying squirrel may have high susceptibility to infection.…”