Functional Characterization of an Interferon Gamma Receptor-Like Protein on Entamoeba histolytica

Pulido-Ortega, Julieta; Talamás‐Rohana, Patricia; Muñoz‐Ortega, Martín Humberto; Aldaba‐Muruato, Liseth Rubí; Martínez-Hernández, Sandra Luz; Campos-Esparza, María del Rosario; Cervantes‐García, Daniel; Leon‐Coria, Aralia; Chadee, Kris; Ventura‐Juárez, Javier

doi:10.1128/iai.00540-19

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…It is widely known, that E. histolytica can respond to diverse humoral factors like IL-8, IFN-γ, TNF-α, and IL-1β ( Zhang et al., 2000 ; Pfaff et al., 2003 ; Blazquez et al., 2008 ; Pulido-Ortega et al., 2019 ), modulating its capability to cause damage. In this sense, for the first time we are reporting a direct response of the ameba to a neurotransmitter, throughout the binding of ACh to E. histolytica trophozoites membrane.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine Upregulates Entamoeba histolytica Virulence Factors, Enhancing Parasite Pathogenicity in Experimental Liver Amebiasis

Medina-Rosales

Muñoz‐Ortega

García-Hernández

et al. 2021

Front. Cell. Infect. Microbiol.

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Entamoeba histolytica is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of E. histolytica to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes acetylcholine (ACh) as one of the predominant neurotransmitters at the infection site. Consequently, the response of E. histolytica trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on E. histolytica virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to E. histolytica pathogenesis, and assessment of the capability of E. histolytica to migrate and form hepatic abscesses in hamsters. Results demonstrated that E. histolytica trophozoites bind ACh on their membrane and show a clear increase of the expression of virulence factors, that were upregulated upon stimulation with the neurotransmitter. ACh treatment increased the expression of L220, Gal/GalNAc lectin heavy subunit (170 kDa), amebapore C, cysteine proteinase 2 (ehcp-a2), and cysteine proteinase 5 (ehcp-a5). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive amebiasis.

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Section: Discussionmentioning

confidence: 99%

Acetylcholine Upregulates Entamoeba histolytica Virulence Factors, Enhancing Parasite Pathogenicity in Experimental Liver Amebiasis

Medina-Rosales

Muñoz‐Ortega

García-Hernández

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Therefore, a series of E. histolytica -secreted molecules bind to PRRs on immune cells in the lamina propria of the intestine, activating the inflammatory pathway ( 9 ). Peroxiredoxin that has potent antioxidant activity localized in the cytoplasm of trophozoites can protect E. histolytica from ROS-induced damage ( 15 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal epithelial cells are intact at the early stages of inflammation; the binding of Gal/GalNAc lectin to colonic epithelial cells allows surface bound EhCP5 to ligate avb3 integrin that leads to NF-kB activation and pro-inflammatory responses. Then, CP5 from E. histolytica activates extracellular pro-IL-1b which, in addition to the chemoattractant secreted by epithelial cells, recruits neutrophils and macrophages, resulting in a serious inflammatory reaction (27). Therefore, a series of E. histolytica-secreted molecules bind to PRRs on immune cells in the lamina propria of the intestine, activating the inflammatory pathway (9).…”

Section: Discussionmentioning

confidence: 99%

A Novel TLR4-Binding Domain of Peroxiredoxin From Entamoeba histolytica Triggers NLRP3 Inflammasome Activation in Macrophages

Feng

Zhao

et al. 2021

Front. Immunol.

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Macrophages promote early host responses to infection by releasing pro-inflammatory cytokines, and they are crucial to combat amoebiasis, a disease affecting millions of people worldwide. Macrophages elicit pro-inflammatory responses following direct cell/cell interaction of Entamoeba histolytica, inducing NLRP3 inflammasome activation with high-output IL-1β/IL-18 secretion. Here, we found that trophozoites could upregulate peroxiredoxins (Prx) expression and abundantly secrete Prxs when encountering host cells. The C-terminal of Prx was identified as the key functional domain in promoting NLRP3 inflammasome activation, and a recombinant C-terminal domain could act directly on macrophage. The Prxs derived from E. histolytica triggered toll-like receptor 4-dependent activation of NLRP3 inflammasome in a cell/cell contact-independent manner. Through genetic, immunoblotting or pharmacological inhibition methods, NLRP3 inflammasome activation was induced through caspase-1-dependent canonical pathway. Our data suggest that E. histolytica Prxs had stable and durable cell/cell contact-independent effects on macrophages following abundantly secretion during invasion, and the C-terminal of Prx was responsible for activating NLRP3 inflammasome in macrophages. This new alternative pathway may represent a potential novel therapeutic approach for amoebiasis, a global threat to millions.

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“…Human heterologous antibodies have been a powerful tool to study and identify related proteins to parasites pathogenicity, recognizing proteins that are not identical to those present in higher eukaryotes but that are localized and function as the ones looked for (Estrada‐Figueroa et al, 2018; Flores‐Robles, Rosales, Rosales‐Encina, & Talamás‐Rohana, 2003; Pulido‐Ortega et al, 2019; Talamás‐Rohana, Hernández‐Ramírez, Pérez‐García, & Ventura‐Juárez, 1998). Although there are no homologous genes for GM130 and TGN38 in amoebae, a clear recognition of these antibodies was detected by immunoelectron, confocal microcopy and Western blot.…”

Section: Discussionmentioning

confidence: 99%

Golgi apparatus components in Entamoeba histolytica and Entamoeba dispar after monensin treatment

Talamás‐Lara

Acosta-Virgen

Chávez‐Munguía

et al. 2021

Microscopy Res & Technique

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Highly dynamic ribosomes, glycogen granules, thinly fibrillar material, and multiple membrane-bound vesicles are embedded in the matrix-rich cytoplasm of Entamoeba spp. trophozoites. The absence of a Golgi apparatus in these amoebae has been commonly accepted. Here we challenge this observation by incubating Entamoeba histolytica and Entamoeba dispar with monensin, an ionophore that produces swelling of the Golgi apparatus. We observe changes in the trophozoites through standard transmission electron microscopy, cryofixation and cryosubstitution, and analyze the label and expression of known resident proteins of the cis-GM130 and trans-TGN38 Golgi network through confocal microscopy and Western blot assays. Cryosubstitution and standard methods using the treatment, preserved membranous lamellae resembling Golgi components. GM130 and TGN38 Golgi antigens were found by immunoelectron, immunoblot, and co-localization by confocal microscopy using the reagent NBD C6-ceramide. Our results indicate that previously undetected Golgi apparatus components are present in the cytoplasm of E. histolytica and E. dispar.

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Functional Characterization of an Interferon Gamma Receptor-Like Protein on Entamoeba histolytica

Cited by 9 publications

References 51 publications

Acetylcholine Upregulates Entamoeba histolytica Virulence Factors, Enhancing Parasite Pathogenicity in Experimental Liver Amebiasis

Acetylcholine Upregulates Entamoeba histolytica Virulence Factors, Enhancing Parasite Pathogenicity in Experimental Liver Amebiasis

A Novel TLR4-Binding Domain of Peroxiredoxin From Entamoeba histolytica Triggers NLRP3 Inflammasome Activation in Macrophages

Golgi apparatus components in Entamoeba histolytica and Entamoeba dispar after monensin treatment

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