New insights into Entamoeba histolytica pathogenesis

Baxt, Leigh A.; Singh, Upinder

doi:10.1097/qco.0b013e32830ce75f

Cited by 57 publications

(34 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, it is likely that at early time points during infection (i.e., at 12 h) transcriptional changes are due to superficial invasion of the mucosa, while later responses represent deeper invasion and more tissue damage. Along with amebic invasion, immune infiltration occurs in distinct phases, with neutrophils recruited early and macrophage recruitment and granuloma formation occurring later (68,70). Thus, the data support the dynamic nature of both E. histolytica invasion and also the adapting host inflammatory response.…”

Section: Discussionsupporting

confidence: 55%

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

et al. 2013

View full text Add to dashboard Cite

dResistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues were analyzed for changes in gene expression. By 72 h postchallenge, all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. Thirty-seven genes were differentially expressed in response to infection at 72 h, including proinflammatory genes (CXCL2, S100A8/9, PLA2G7, ITBG2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h postchallenge of infected Q223 versus R223 mice identified a subset of differentially expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide into this previously uncharacterized mechanism of mucosal immunity.T he association of leptin signaling with infectious diseases has long been suspected; however, only recently was the significant association between leptin and human disease described (1-4). It was determined that a common genetic mutation of the leptin receptor (LEPR), Q223R, was associated with an approximately 4-fold increase in likelihood of infection with Entamoeba histolytica in a Bangladeshi cohort of children (4). The murine model of amebiasis recapitulated the human findings, demonstrating that 223R (homozygous for arginine) mice were significantly more susceptible to infection with E. histolytica than Q223 (homozygous for glutamine) mice. In addition, both ob/ob (leptin Ϫ/Ϫ ) and db/db (LEPR Ϫ/Ϫ ) mice had increased rates of E. histolytica infection and worse tissue destruction and mortality. Finally, the use of tissue-specific LEPR knockouts demonstrated that the site of action for LEPR was located within the intestinal epithelial cell (IEC) population (5).LEPR belongs to the gp130 family of cytokine receptors. Upon leptin binding to the homodimeric LEPR, Janus kinase 2 (JAK2) is activated, leading to the phosphorylation of tyrosines 985, 1077, and 1138 on LEPR, which in turn are recognized by Src homology 2 domain-containing tyrosine phosphatase (SHP2) and suppressor of cytokine signaling 3 (SOCS3), STAT5a/b, and STAT3 (respectively) (6)(7)(8). Murine studies demonstrated that signal...

show abstract

Section: Discussionsupporting

confidence: 55%

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Islands of better preserved liver tissue were also seen scattered among the necrotic foci. Moreover, serum sample could easily be obtained from [5][6][7] days post-infected hamster, and contained sufficient polyclonal antibodies that recognize E. histolytica trophozoites [20] .…”

Section: Discussionmentioning

confidence: 99%

“…It develops through the hematological dissemination of the pathogenic trophozoites into liver via the tributaries of portal vein after invasion of colonic mucosa, resulting in the formation of solitary or multiple abscesses regularly found in the right liver lobe [4] . The common virulence factors involved include Gal/GalNAc specific lectin, cysteine proteinases, amoebapores and lipophosphopeptidoglycan molecules [5,6] . In the formation of ALA, the general sequence of morphological changes in liver tissues involves acute inflammation where the acute cellular infiltration is composed of polymorphonuclear leukocytes which surround the centrally located amoebas, then progress to granuloma formation after the leukocytes were being replaced by macrophages and epithelioid cells and subsequently…”

Section: Introductionmentioning

confidence: 99%

Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods

Ning

Kin

Mustafa

et al. 2012

Asian Pacific Journal of Tropical Biomedicine

View full text Add to dashboard Cite

“…In addition, coculture with enteropathogenic bacteria has recently been mentioned as a virulence exacerbation inductor (Galván-Moroyoqui et al, 2008). In this context, the role of gene activation is a subject of particular interest in the study of the E. histolytica virulence determinants (Baxt and Singh, 2008). Differential gene expression (Bruchhaus et al, 2002) and increased erythrophagocytosis capacity (Balderas-Renteria et al, 2007) have been reported in trophozoites recovered from these experimental liver lesions, in contrast with trophozoites that have been continuously cultured under axenical conditions.…”

Section: Introductionmentioning

confidence: 96%

Entamoeba histolyticaelectrondense granules secretion in vitro and in vivo: Ultrastructural study

Chávez‐Munguía¹,

Castañón²,

Hernández‐Ramírez³

et al. 2011

Microscopy Res & Technique

View full text Add to dashboard Cite

Electron dense granules (EDGs) were identified by transmission electron microscopy in Entamoeba histolytica trophozoites recovered from hamster liver lesions. Abundant granules were present in trophozoites recovered after 15 min of liver inoculation. Variation in the size and morphology of these EDGs was also observed. Numerous granules were present in the plasma membrane when these parasites were incubated for 5 min with MDCK monolayers. Release of these EDGs was suggested by the presence of granules in contact with the surface of the target cell plasma membrane. Parasite phagocytic invaginations were observed after 10 min of parasite-monolayer interaction. In these structures, scarce granules were seen. Granules secretion was corroborated by obtaining of a pellet of these small structures from the incubation of trophozoites with collagen supernatant. Collagenase and gellatinase activity of this pellet was identified in SDS-PAGE gels. EDGs were also present in amebic hamster liver lesions. Our observations corroborate that these granules are secreted and suggest that may participate in the cytopathic effect of E. histolytica both in vitro and in vivo.

show abstract

New insights into Entamoeba histolytica pathogenesis

Cited by 57 publications

References 43 publications

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods

Entamoeba histolyticaelectrondense granules secretion in vitro and in vivo: Ultrastructural study

Contact Info

Product

Resources

About