Research Article: Differential Release and Phagocytosis of Tegument Glycoconjugates in Neurocysticercosis: Implications for Immune Evasion Strategies

Date Published: April 9, 2008

Publisher: Public Library of Science

Author(s): Jorge I. Alvarez, Jennifer Rivera, Judy M. Teale, Malcolm Jones

Abstract: Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) by the metacestode of the helminth Taenia solium. The severity of the symptoms is associated with the intensity of the immune response. First, there is a long asymptomatic period where host immunity seems incapable of resolving the infection, followed by a chronic hypersensitivity reaction. Since little is known about the initial response to this infection, a murine model using the cestode Mesocestoides corti (syn. Mesocestoides vogae) was employed to analyze morphological changes in the parasite early in the infection. It was found that M. corti material is released from the tegument making close contact with the nervous tissue. These results were confirmed by infecting murine CNS with ex vivo–labeled parasites. Because more than 95% of NCC patients exhibit humoral responses against carbohydrate-based antigens, and the tegument is known to be rich in glycoconjugates (GCs), the expression of these types of molecules was analyzed in human, porcine, and murine NCC specimens. To determine the GCs present in the tegument, fluorochrome-labeled hydrazides as well as fluorochrome-labeled lectins with specificity to different carbohydrates were used. All the lectins utilized labeled the tegument. GCs bound by isolectinB4 were shed in the first days of infection and not resynthesized by the parasite, whereas GCs bound by wheat germ agglutinin and concavalinA were continuously released throughout the infectious process. GCs bound by these three lectins were taken up by host cells. Peanut lectin-binding GCs, in contrast, remained on the parasite and were not detected in host cells. The parasitic origin of the lectin-binding GCs found in host cells was confirmed using antibodies against T. solium and M. corti. We propose that both the rapid and persistent release of tegumental GCs plays a key role in the well-known immunomodulatory effects of helminths, including immune evasion and life-long inflammatory sequelae seen in many NCC patients.

Partial Text: Neurocysticercosis (NCC), caused by the larval form of the tapeworm T. solium, is one of the most common parasitic infections of the CNS worldwide [1],[2]. Although the metacestodes reach their mature size within a few weeks, evidence indicates that prior to clinical manifestations, there is a long asymptomatic period (months or even years) thought to be the result of numerous mechanisms that the organism uses to modulate and inhibit the immune response [3]. Eventually, clinical symptoms appear and include headache, seizures, and hydrocephalus that can be devastating and lifelong. Symptoms are normally associated with chronic inflammatory responses suggesting a source of persistent antigen [2],[4]. Thus, immune evasion and persistent antigen appear to be important characteristics of this disease process.

In this study we describe the composition, changes and release during infection of the T. solium and M. corti tegument. The results show that the tegument of these helminths changes morphologically and biochemically as the parasites interact with the host microenvironment. Early in the infection, IB4 bound molecules are lost from the tegument whereas molecules bound by WGA are continuously released from this structure during infection. In addition, the material released from the tegument is found in infiltrating leukocytes that we have characterized extensively in previous studies [6], [7], [9]–[11]. The mechanisms used by T. solium metacestodes to establish a chronic infection in the human CNS remain poorly elucidated. Because of their macroscopic size, helminths utilize elaborate mechanisms to manipulate the host immune response and to ensure long term survival. One of the structures involved in sustaining such immunoregulation appears to be the tegument that is subject to damage under host response [32]. Analyses of M. corti metacestodes injected in the mouse brain revealed that the tegument of these parasites is partially lost as the parasite moves into the CNS. This is consistent with studies in trematodes like Schistosoma sp., in which the first larval form or miracidium is covered with a thick glycocalix coat that after penetration in the intermediate host gets considerably thinner [33].



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