Host Immune Response to Intestinal Amebiasis

Moonah, Shannon; Jiang, Nona M.; Petri, William A.

doi:10.1371/journal.ppat.1003489

Cited by 81 publications

(79 citation statements)

References 37 publications

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“…histolytica invasion results in a mucosal inflammatory response, inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages (Begum et al, ), whereas TNF‐α stimulates neutrophils and macrophages to release ROS and NO to fight the parasite. An excess of TNF‐α can result in direct damage to host tissues (Moonah, ). In vitro experiments involving exposure of cultured human bronchial epithelial cells to inflammatory cytokines revealed that TNF‐α treatment resulted in the internalisation and a decreased expression of Dsg‐2 (Zuckerman, ), evidencing differential response to distinct stimuli.…”

Section: Resultsmentioning

confidence: 99%

Adherens junctions and desmosomes are damaged byEntamoeba histolytica:Participation of EhCPADH complex and EhCP112 protease

Hernández-Nava

Cuellar

Nava

et al. 2017

Cellular Microbiology

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Entamoeba histolytica trophozoites adhere to epithelium at the cell-cell contact and perturb tight junctions disturbing the transepithelial electrical resistance. Behind tight junctions are the adherens junctions (AJs) that reinforce them and the desmosomes (DSMs) that maintain the epithelium integrity. The damage produced to AJs and DMSs by this parasite is unknown. Here, we studied the effect of the trophozoites, the EhCPADH complex, and the EhCP112 recombinant enzyme (rEhCP112) on AJ and DSM proteins. We found that trophozoites degraded β-cat, E-cad, Dsp l/ll, and Dsg-2 with the participation of EhCPADH and EhCP112. After contact of epithelial cells with trophozoites, immunofluorescence and transmission electron microscopy assays revealed EhCPADH and rEhCP112 at the intercellular space where they colocalised with β-cat, E-cad, Dsp l/ll, and Dsg-2. Moreover, our results suggested that rEhCP112 could be internalised by caveolae and clathrin-coated vesicles. Immunoprecipitation assays showed the interaction of EhCPADH with β-cat and Dsp l/ll. Besides, in vivo assays demonstrated that rEhCP112 concentrates at the cellular borders of the mouse intestine degrading E-cad and Dsp I/II. Our research gives the first clues on the trophozoite attack to AJs and DSMs and point out the role of the EhCPADH and EhCP112 in the multifactorial event of trophozoites virulence.

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Section: Resultsmentioning

confidence: 99%

Adherens junctions and desmosomes are damaged byEntamoeba histolytica:Participation of EhCPADH complex and EhCP112 protease

Hernández-Nava

Cuellar

Nava

et al. 2017

Cellular Microbiology

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“…EhMIF might therefore perform a function similar to that of Plasmodium MIF, rendering the host susceptible to reinfection by the parasite. Furthermore, E. histolytica has developed an impressive number of mechanisms to evade the host immune response (4). For example, the amebic surface protein peroxiredoxin possesses antioxidant activity, which protects the parasite from immune cell reactive oxygen species (60).…”

Section: Fig 3 Ehmif Immunomodulates Macrophages (A)mentioning

confidence: 99%

“…Infection with E. histolytica trophozoites results in marked mucosal inflammation. Along with E. histolytica cytolytic factors, the host inflammatory response contributes to the tissue destruction seen in amebic colitis (4). Tumor necrosis factor alpha (TNF-␣) is a proinflammatory cytokine that plays a central role in intestinal inflammation, including the gut inflammation seen in amebic colitis.…”

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confidence: 99%

The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages

et al. 2014

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bThe host inflammatory response contributes to the tissue damage that occurs during amebic colitis, with tumor necrosis factor alpha (TNF-␣) being a key mediator of the gut inflammation observed. Mammalian macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the exacerbation of a wide range of inflammatory diseases, including colitis. We identified a MIF gene homolog in the Entamoeba histolytica genome, raising the question of whether E. histolytica MIF (EhMIF) has proinflammatory activity similar to that of mammalian MIF. In this report, we describe the first functional characterization of EhMIF. Antibodies were prepared against recombinantly expressed EhMIF and used to demonstrate that EhMIF is expressed as a 12-kDa protein localized to the cytoplasm of trophozoites. In a manner similar to that of mammalian MIF, EhMIF interacted with the MIF receptor CD74 and bound to macrophages. EhMIF induced interleukin-6 (IL-6) production. In addition, EhMIF enhanced TNF-␣ secretion by amplifying TNF-␣ production by lipopolysaccharide (LPS)-stimulated macrophages and by inhibiting the glucocorticoid-mediated suppression of TNF-␣ secretion. EhMIF was expressed during human infection, as evidenced by the presence of anti-EhMIF antibodies in the sera of children living in an area where E. histolytica infection is endemic. Anti-EhMIF antibodies did not cross-react with human MIF. The ability of EhMIF to modulate host macrophage function may promote an exaggerated proinflammatory immune response and contribute to the tissue damage seen in amebic colitis.

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“…The latter, broadly referred to as the eukaryome (Lukes et al, 2015), is comprised of a myriad of fungi, helminths and protists. Several protists are known pathogens of the mouse and human intestine, these include the microsporidia ( Encephalitizoan cuniculi ) (Stentiford et al, 2016), Entamoeba histolytica (Moonah et al, 2013), Toxoplasma gondii (Molloy et al, 2013), Giardia spp. and Cryptosporidium spp.…”

Section: Introductionmentioning

confidence: 99%

Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

Chudnovskiy

Mortha

Kana

et al. 2016

Cell

274

304

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While conventional pathogenic protists have been extensively studied, there is an underappreciated constitutive protist microbiota that is an integral part of the vertebrate microbiome. The impact of these species on the host and their potential contributions to mucosal immune homeostasis remain poorly studied. Here, we show that the protozoan Tritrichomonas musculis activates the host epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18 promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic protection from mucosal bacterial infections. Along with its role as a “protistic” antibiotic, colonization with T. musculis exacerbates the development of T cell driven colitis and sporadic colorectal tumors. Our findings demonstrate a novel mutualistic host-protozoan interaction that increases mucosal host defenses at the cost of an increased risk of inflammatory disease.

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Host Immune Response to Intestinal Amebiasis

Cited by 81 publications

References 37 publications

Adherens junctions and desmosomes are damaged byEntamoeba histolytica:Participation of EhCPADH complex and EhCP112 protease

Adherens junctions and desmosomes are damaged byEntamoeba histolytica:Participation of EhCPADH complex and EhCP112 protease

The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages

Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

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