New insights into host-pathogen interactions during<i>Entamoeba histolytica</i>liver infection

Faust, Daniela M.; Markiewicz, Jacques Marquay; Santi-Rocca, Julien; Guillén, Nancy

doi:10.1556/eujmi.1.2011.1.4

Cited by 10 publications

(8 citation statements)

References 48 publications

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“…Cytoskeletal-associated proteins are intricately and extensively regulated by post-translational modification to regulate cytoskeletal dynamics during many cellular processes such as adhesion, cell death as well as cell-specific functions such as cytokine secretion. Previous studies have shown that Eh in contact with liver sinuisoidal endothelial cells triggers the breakdown of actin stress fibers, and relocalization of cytoskeletal-associated proteins [ 33 , 34 ]. In the setting of macrophage- Eh interactions, phosphorylated paxillin and α 5 β 1 integrin have been shown to concentrate at sites of contact between macrophages and Eh [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

The macrophage cytoskeleton acts as a contact sensor upon interaction with Entamoeba histolytica to trigger IL-1β secretion

St‐Pierre¹,

Moreau²,

Cornick³

et al. 2017

PLoS Pathog

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Entamoeba histolytica (Eh) is the causative agent of amebiasis, one of the major causes of dysentery-related morbidity worldwide. Recent studies have underlined the importance of the intercellular junction between Eh and host cells as a determinant in the pathogenesis of amebiasis. Despite the fact that direct contact and ligation between Eh surface Gal-lectin and EhCP-A5 with macrophage α5β1 integrin are absolute requirements for NLRP3 inflammasome activation and IL-1β release, many other undefined molecular events and downstream signaling occur at the interface of Eh and macrophage. In this study, we investigated the molecular events at the intercellular junction that lead to recognition of Eh through modulation of the macrophage cytoskeleton. Upon Eh contact with macrophages key cytoskeletal-associated proteins were rapidly post-translationally modified only with live Eh but not with soluble Eh proteins or fragments. Eh ligation with macrophages rapidly activated caspase-6 dependent cleavage of the cytoskeletal proteins talin, Pyk2 and paxillin and caused robust release of the pro-inflammatory cytokine, IL-1β. Macrophage cytoskeletal cleavages were dependent on Eh cysteine proteinases EhCP-A1 and EhCP-A4 but not EhCP-A5 based on pharmacological blockade of Eh enzyme inhibitors and EhCP-A5 deficient parasites. These results unravel a model where the intercellular junction between macrophages and Eh form an area of highly interacting proteins that implicate the macrophage cytoskeleton as a sensor for Eh contact that leads downstream to subsequent inflammatory immune responses.

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Section: Resultsmentioning

confidence: 99%

The macrophage cytoskeleton acts as a contact sensor upon interaction with Entamoeba histolytica to trigger IL-1β secretion

St‐Pierre¹,

Moreau²,

Cornick³

et al. 2017

PLoS Pathog

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“…Phagocytosis is a process by which dead cells and large particles such as bacteria are internalized as a whole. Induction of apoptosis to host cells by a contact of E. histolytica has been reported previously (Huston et al ., ; Faust et al ., ). The Gal/GalNAc lectin and cysteine protease A5 are required for phagocytosis (Mann et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…The Gal/GalNAc lectin and cysteine protease A5 are required for phagocytosis (Mann et al ., ). Trophozoites induce apoptosis to host cells by contact (Huston et al ., ; Faust et al ., ), recognize phosphatidylserine exposed on the apoptotic and necrotic host cells (Boettner et al ., ) and internalize them by phagocytosis. In contrast, trogocytosis, recently described by Ralston et al .…”

Section: Introductionmentioning

confidence: 99%

“…The Gal/GalNAc lectin and cysteine protease A5 are required for phagocytosis (Mann et al, 1991). Trophozoites induce apoptosis to host cells by contact (Huston et al, 2003;Faust et al, 2011), recognize phosphatidylserine exposed on the apoptotic and necrotic host cells and internalize them by phagocytosis. In contrast, trogocytosis, recently described by Ralston et al (2014), is a process in which a cell nibbles pieces of a living host cell, eventually leading to death by the loss of membrane integrity and mitochondrial potential (Guillen, 2014;Ralston et al, 2014;Ralston, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Endoplasmic reticulum‐resident Rab8A GTPase is involved in phagocytosis in the protozoan parasiteEntamoeba histolytica

Hanadate

Saito‐Nakano

Nakada‐Tsukui

et al. 2016

Cellular Microbiology

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SummaryPhagocytosis is indispensable for the pathogenesis of the intestinal protozoan parasite Entamoeba histolytica. Here, we showed that in E. histolytica Rab8A, which is generally involved in trafficking from the trans‐Golgi network to the plasma membrane in other organisms but was previously identified in phagosomes of the amoeba in the proteomic analysis, primarily resides in the endoplasmic reticulum (ER) and participates in phagocytosis. We demonstrated that down‐regulation of EhRab8A by small antisense RNA‐mediated transcriptional gene silencing remarkably reduced adherence and phagocytosis of erythrocytes, bacteria and carboxylated latex beads. Surface biotinylation followed by SDS‐PAGE analysis revealed that the surface expression of several proteins presumably involved in target recognition was reduced in the EhRab8A gene‐silenced strain. Further, overexpression of wild‐type EhRab8A augmented phagocytosis, whereas expression of the dominant‐negative form of EhRab8A resulted in reduced phagocytosis. These results indicated that EhRab8A regulates transport of surface receptor(s) for the prey from the ER to the plasma membrane. To our knowledge, this is the first report that the ER‐resident Rab GTPase is involved in phagocytosis through the regulation of trafficking of a surface receptor, supporting a premise of direct involvement of the ER in phagocytosis.

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“…Trophozoites are the invasive form of the parasite and they provoke the symptoms of the disease that could be lethal when it is not properly treated. Cysts are excreted with feces, contaminating water and food that could infect other people [ 4 ]. Trophozoites can be in vitro cultured, but cysts are not generated consistently in the laboratory, hampering the study of the molecular mechanisms that underly the parasite life cycle, postponing the development of novel strategies to erradicate amoebiasis.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

et al. 2016

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Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis.

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New insights into host-pathogen interactions duringEntamoeba histolyticaliver infection

Cited by 10 publications

References 48 publications

The macrophage cytoskeleton acts as a contact sensor upon interaction with Entamoeba histolytica to trigger IL-1β secretion

The macrophage cytoskeleton acts as a contact sensor upon interaction with Entamoeba histolytica to trigger IL-1β secretion

Endoplasmic reticulum‐resident Rab8A GTPase is involved in phagocytosis in the protozoan parasiteEntamoeba histolytica

Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

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