Complement is a rat natural resistance factor to amoebic liver infection

Abstract

Amoebiasis is a parasitic disease caused by Entamoeba histolytica. This illness is prevalent in poor countries causing 100,000 deaths worldwide. Knowledge of the natural resistance mechanisms of rats to amoebic liver abscess (ALA) development may help to discover new pathogenic factors and to design novel therapeutic strategies against amoebiasis. In this work, histologic analyses suggested that the complement system may play a central role in rat natural resistance to ALA. E. histolytica trophozoites disappeared from rat liver within 6 h post-infection with minimal or no inflammatory infiltrate. In vitro findings indicate that rat complement was lethal for the parasite. Furthermore, hamsters became resistant to ALA by intravenous administration of fresh rat serum before infection. The amoebicidal potency of rat complement was 10 times higher than hamster complement and was not related to their respective CH50 levels. The alternative pathway of complement plays a central role in its toxicity to E. histolytica since trypan blue, which is a C3b receptor inhibitor, blocks its amoebicidal activity. These results suggest that amoebic membrane affinity, high for C3b and/or low for Factor H, in comparison with the hamster ones, may result in higher deposition of membrane complex attack on parasite surface and death.

Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion of Lysis by Human Serum

“…Amoebic cysteine proteinases play a role in cleavage of complement components (50–52). Amoebae are also made temporarily resistant to complement lysis through treatment with increasing doses of heat-inactivated human serum, though the mechanism remains unclear (37, 53), and it was recently found that amoebae do not develop resistance to serum from rats by this method (54). As the percentage of amoebae lysed after exposure to human serum in our assays never reached 100%, even under conditions where amoebae were incubated alone, it is likely that multiple factors contribute to complement resistance in E.…”

Mechanisms of natural resistance of Balb/c mice to experimental liver amoebiasis

“…The potent amoebicidal activity of complement in Wistar rats is responsible for parasite elimination before 6 h [5]. In contrast, the amoebicidal activity of complement in Balb/c mouse is not involved in the parasite clearance from liver since hypocomplementemia did not modify the survival time of the parasite (72 h).…”

“…Innate immunity may play an important role in such resistance since in most of them the parasite is cleared before the specific immune response. Recently, it was determined that serum complement of Wistar rats is lethal for the parasite and is involved in their resistance to EALA [5]. Furthermore, Balb/c mice have been used to study the EALA development; however, contrasting results have been published showing early as well as late clearance of the parasites (from 1 to 7 days) [6–10].…”

Trogocytosis by Entamoeba histolytica mediates acquisition and display of human cell membrane proteins and evasion of lysis by human serum

“…Amoebic cysteine proteinases play a role in cleavage of complement components [50–52]. It has also been reported that amoebae are made temporarily resistant to complement lysis through treatment with increasing doses of heat-inactivated human serum, though the mechanism remains unclear [37,53], and it was recently found that amoebae do not develop resistance to serum from rats by this method [54]. As the percentage of amoebae lysed after exposure to human serum in our assays never reached 100%, even in conditions where amoebae were incubated alone, it is likely that multiple factors contribute to complement resistance in E. histolytica.…”