Entamoeba histolyticaandE. disparCalreticulin: Inhibition of Classical Complement Pathway and Differences in the Level of Expression in Amoebic Liver Abscess

Abstract

The role of calreticulin (CRT) in host-parasite interactions has recently become an important area of research. Information about the functions of calreticulin and its relevance to the physiology of Entamoeba parasites is limited. The present work demonstrates that CRT of both pathogenic E. histolytica and nonpathogenic E. dispar species specifically interacted with human C1q inhibiting the activation of the classical complement pathway. Using recombinant EhCRT protein, we demonstrate that CRT interaction site and human C1q is located at the N-terminal region of EhCRT. The immunofluorescence and confocal microscopy experiments show that CRT and human C1q colocalize in the cytoplasmic vesicles and near to the surface membrane of previously permeabilized trophozoites or are incubated with normal human serum which is known to destroy trophozoites. In the presence of peripheral mononuclear blood cells, the distribution of EhCRT and C1q is clearly over the surface membrane of trophozoites. Nevertheless, the level of expression of CRT in situ in lesions of amoebic liver abscess (ALA) in the hamster model is different in both Entamoeba species; this molecule is expressed in higher levels in E. histolytica than in E. dispar. This result suggests that EhCRT may modulate some functions during the early moments of the host-parasite relationship.

Differential expression of pathogenic genes of Entamoeba histolytica vs E. dispar in a model of infection using human liver tissue explants

“…cruzi CRT to specifically bind to the C1q component of the classic pathway of serum complement in an infected host, thus inhibiting the activation of this immune response amplification system [ 47 ].The same mechanism has also been described for E . histolytica trophozoites [ 49 ]. Additionally, the interaction between C1q and trophozoites previously stimulated with Jurkat cells leads to a C1q-CRT interaction on the membrane of the trophozoites [ 50 ].…”

Entamoeba histolytica Calreticulin Induces the Expression of Cytokines in Peripheral Blood Mononuclear Cells Isolated From Patients With Amebic Liver Abscess

“…The immunohistochemical assays on trophozoites show that Eh CRT is in cytoplasmic vesicles and in vesicles that are in close contact with the inner cytoplasmic membrane (González et al, 2011 ). In addition, it was demonstrated that the CRT from both pathogenic E. histolytica and nonpathogenic E. dispar species specifically interact with human C1q molecules and inhibit the activation of the classical complement pathway (Ximénez et al, 2014 ). This activity is consistent with that reported by Vaithilingam et al ( 2012 ).…”

Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

“…37 In addition, ameba developed an evasion mechanism against the host immune responses, by expressing the ER-associated calreticulin, which inhibited the classical serum complement pathway. 38 This showed that calreticulin may play a significant role in the host-parasite relationship during the early infection phases. 38 Therefore, we postulate that the increased abundance of calreticulin in the vEh variant of E. histolytica may indicate its involvement in the regulatory mechanism in relation to pathogenesis between the host and the parasite to ensure its successful survival in the host.…”