Host Protective Mechanisms to Intestinal Amebiasis

Mj, Uddin; Leslie, Jhansi L.; Petri, William A.

doi:10.1016/j.pt.2020.09.015

Cited by 19 publications

(14 citation statements)

References 94 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the large intestine, trophozoites can live without eliciting symptoms of disease, while feeding on commensal bacteria, 42 erythrocytes, 51 and dead cells 52 . However, some more pathogenic trophozoites can degrade the mucosal layer, adhere to the epithelium, invade tissues and disseminate to other organs 44,53–55 . The circumstances favoring these changes in amoeba behavior are still undiscovered.…”

Section: Pathogenesis Of Amoebiasismentioning

confidence: 99%

Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica

Rosales

2021

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Entamoeba histolytica is a protozoan parasite with high prevalence in developing countries, and causes amoebiasis. This disease affects the intestine and the liver, and is the third leading cause of human deaths among parasite infections. E. histolytica infection of the intestine or liver is associated with a strong inflammation characterized by a large number of infiltrating neutrophils. Consequently, several reports suggest that neutrophils play a protective role in amoebiasis. However, other reports indicate that amoebas making direct contact with neutrophils provoke lysis of these leukocytes, resulting in the release of their lytic enzymes, which in turn provoke tissue damage. Therefore, the role of neutrophils in this parasitic infection remains controversial. Neutrophils migrate from the circulation to sites of infection, where they display several antimicrobial functions, including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NET). Recently, it was found that E. histolytica trophozoites are capable of inducing NET formation. Neutrophils in touch with amoebas launched NET in an explosive manner around the amoebas and completely covered them in nebulous DNA and cell aggregates where parasites got immobilized and killed. In addition, the phenotype of neutrophils can be modified by the microbiome resulting in protection against amoebas. This review describes the mechanisms of E. histolytica infection and discusses the novel view of how neutrophils are involved in innate immunity defense against amoebiasis. Also, the mechanisms on how the microbiome modulates neutrophil function are described.

show abstract

Section: Pathogenesis Of Amoebiasismentioning

confidence: 99%

Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica

Rosales

2021

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint this version posted June 15, 2021. ; https://doi.org/10.1101/2021.06.14.448450 doi: bioRxiv preprint 9 expanded in vitro and activated in the presence of IL-33 [5,13,14]. ST2+ ILC2s were flow-sorted and adoptively transferred into RAG2 -/γc -/mice (5×10 5 cells/mouse) through intraperitoneal injection.…”

Section: Adoptive Transfer Of Ilc2s Restored Il-33 Mediated Protection In Rag2 -/γC -/Micementioning

confidence: 99%

“…ILC2s were isolated from mouse spleen, mesenteric lymph node, and colonic tissue and enriched using magnetic cell separation. Isolated cells were then expanded in vitro and activated in the presence of IL-33 [5,13,14]. ST2+ ILC2s were flow-sorted and adoptively transferred into RAG2 -/γc -/mice (5×10 cells/mouse) through intraperitoneal injection.…”

Section: Adoptive Transfer Of Ilc2s Restored Il-33 Mediated Protection In Rag2 -/γC -/Micementioning

confidence: 99%

The IL-33-ILC2 pathway protects from amebic colitis

Uddin

Leslie

Burgess

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage during infection. Treatment with recombinant IL-33 protected mice from amebic infection and colonic tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to infection and weight loss. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the colon. Type 2 immune responses, which are known to be involved in tissue repair, were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2-/- mice but not RAG2-/-γc-/- mice, demonstrating that IL-33 mediated protection occurred in the absence of T or B cells but required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2-/- mice. Adoptive transfer of ILC2s to RAG2-/-γc-/- mice restored IL-33 mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

show abstract

“…Over 65,000 lethal cases of amoebiasis per year have been reported worldwide [1,2], and E. histolytica prevalence has been estimated to reach 3.55% globally [3]. E. histolytica colonizes the human large intestine, and upon a not-well-understood trigger, the trophozoites invade the mucous barrier and cause dysentery and eventually extraintestinal amoebiasis [4]. Due to its adaptation to oxygen-poor environments and its parasitic lifestyle, the cellular organelles and metabolism of E. histolytica are highly modified [5].…”

Section: Introductionmentioning

confidence: 99%

“…E . histolytica colonizes the human large intestine, and upon a not-well-understood trigger, the trophozoites invade the mucous barrier and cause dysentery and eventually extraintestinal amoebiasis [ 4 ]. Due to its adaptation to oxygen-poor environments and its parasitic lifestyle, the cellular organelles and metabolism of E .…”

Section: Introductionmentioning

confidence: 99%

Anaerobic peroxisomes in Entamoeba histolytica metabolize myo-inositol

et al. 2021

View full text Add to dashboard Cite

Entamoeba histolytica is believed to be devoid of peroxisomes, like most anaerobic protists. In this work, we provided the first evidence that peroxisomes are present in E. histolytica, although only seven proteins responsible for peroxisome biogenesis (peroxins) were identified (Pex1, Pex6, Pex5, Pex11, Pex14, Pex16, and Pex19). Targeting matrix proteins to peroxisomes is reduced to the PTS1-dependent pathway mediated via the soluble Pex5 receptor, while the PTS2 receptor Pex7 is absent. Immunofluorescence microscopy showed that peroxisomal markers (Pex5, Pex14, Pex16, Pex19) are present in vesicles distinct from mitosomes, the endoplasmic reticulum, and the endosome/phagosome system, except Pex11, which has dual localization in peroxisomes and mitosomes. Immunoelectron microscopy revealed that Pex14 localized to vesicles of approximately 90–100 nm in diameter. Proteomic analyses of affinity-purified peroxisomes and in silico PTS1 predictions provided datasets of 655 and 56 peroxisomal candidates, respectively; however, only six proteins were shared by both datasets, including myo-inositol dehydrogenase (myo-IDH). Peroxisomal NAD-dependent myo-IDH appeared to be a dimeric enzyme with high affinity to myo-inositol (Km 0.044 mM) and can utilize also scyllo-inositol, D-glucose and D-xylose as substrates. Phylogenetic analyses revealed that orthologs of myo-IDH with PTS1 are present in E. dispar, E. nutalli and E. moshkovskii but not in E. invadens, and form a monophyletic clade of mostly peroxisomal orthologs with free-living Mastigamoeba balamuthi and Pelomyxa schiedti. The presence of peroxisomes in E. histolytica and other archamoebae breaks the paradigm of peroxisome absence in anaerobes and provides a new potential target for the development of antiparasitic drugs.

show abstract

Host Protective Mechanisms to Intestinal Amebiasis

Cited by 19 publications

References 94 publications

Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica

Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica

The IL-33-ILC2 pathway protects from amebic colitis

Anaerobic peroxisomes in Entamoeba histolytica metabolize myo-inositol

Contact Info

Product

Resources

About