Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica

ABSTRACTIt is not understood why only some infections withEntamoeba histolyticaresult in disease. The calcium-regulated transcription factor upstream regulatory element 3-binding protein (URE3-BP) was initially identified by virtue of its role in regulating the expression of two amebic virulence genes, the Gal/GalNac lectin and ferredoxin. Here we tested whether this transcription factor has a broader role in regulating virulence. A comparison ofin vivotoin vitroparasite gene expression demonstrated that 39% ofin vivoregulated transcripts contained the URE3 motif recognized by URE3-BP, compared to 23% of all promoters (P< 0.0001). Amebae induced to express a dominant positive mutant form of URE3-BP had an increase in an elongated morphology (30% ± 6% versus 14% ± 5%;P= 0.001), a 2-fold competitive advantage at invading the intestinal epithelium (P= 0.017), and a 3-fold increase in liver abscess size (0.1 ± 0.1 g versus 0.036 ± 0.1 g;P= 0.03). These results support a role for URE3-BP in virulence regulation.IMPORTANCEAmebic dysentery and liver abscess are caused byEntamoeba histolytica. Amebae colonize the colon and cause disease by invading the intestinal epithelium. However, only one in fiveE. histolyticainfections leads to disease. The factors that govern the transition from colonization to invasion are not understood. The transcription factor upstream regulatory element 3-binding protein (URE3-BP) is a calcium-responding regulator of theE. histolyticaGal/GalNAc lectin and ferredoxin genes, both implicated in virulence. Here we discovered that inducible expression of URE3-BP changed trophozoite morphology and promoted parasite invasion in the colon and liver. These results indicate that one determinant of virulence is transcriptional regulation by URE3-BP.

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Prevalence of Entamoeba histolytica among enteric infection in Al-Furat general hospital in Baghdad/Iraq

10.1063/5.0066967 ◽

2022 ◽

Author(s):

Hanan J. Nayyef ◽

Faheema J. Abo-Alhur ◽

Sinai W. Mohammed ◽

Estabraq A. Taqi ◽

Samer S. Kahdim

Keyword(s):

General Hospital ◽

Entamoeba Histolytica ◽

Enteric Infection

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Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis

mBio ◽

10.1128/mbio.01817-14 ◽

2014 ◽

Vol 5 (6) ◽

Cited By ~ 67

Author(s):

Stacey L. Burgess ◽

Erica Buonomo ◽

Maureen Carey ◽

Carrie Cowardin ◽

Caitlin Naylor ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Entamoeba Histolytica ◽

Murine Model ◽

Inflammatory Diseases ◽

Human Microbiome ◽

Intestinal Bacteria ◽

Enteric Infection ◽

Content Type ◽

Interleukin 17A

ABSTRACTThere is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection.Entamoeba histolyticais a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensalClostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolyticainfection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB+to an SFB−mouse was sufficient to provide protection againstE. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.IMPORTANCEEntamoeba histolyticais the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of theClostridiaknown as SFB provides protection againstE. histolyticaand that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments.

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Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during Entamoeba histolytica Infection

mBio ◽

10.1128/mbio.02046-14 ◽

2014 ◽

Vol 5 (6) ◽

Cited By ~ 21

Author(s):

Caitlin Naylor ◽

Stacey Burgess ◽

Rajat Madan ◽

Erica Buonomo ◽

Khadija Razzaq ◽

...

Keyword(s):

Entamoeba Histolytica ◽

Leptin Receptor ◽

Neutrophil Infiltration ◽

Neutrophil Function ◽

Enteric Infection ◽

Neutrophil Chemotaxis ◽

Content Type ◽

Innate Defense ◽

The Impact ◽

Increased Susceptibility

ABSTRACTAmebiasis is an enteric infection caused byEntamoeba histolytica, with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans with the Q223R leptin receptor mutation have increased susceptibility to amebiasis, but the mechanism has been unclear. Using a mouse model expressing the mutation, we tested the impact of the Q223R mutation on the innate immune response toE. histolyticainfection. The 223R mutation resulted in delayed clearance of amebae from the cecum, as had been previously observed. We found that neutrophil influx to the site of the infection was reduced 12 h after infection in 223R mice. Depletion of neutrophils with anti-Ly6G monoclonal antibody increased susceptibility of wild-type mice to infection, supporting the importance of neutrophils in innate defense. Leptin expression was increased in the cecum byE. histolyticainfection, suggesting that leptin could serve as a homing signal for neutrophils to the gut. Interestingly, neutrophils from mice with the 223R mutation had diminished chemotaxis toward leptin. This impaired chemotaxis likely explained the reduced gut infiltration of neutrophils. The newly recognized effect of the leptin receptor Q223R mutation on neutrophil chemotaxis and the impact of this mutation on multiple infectious diseases suggest a broader impact of this mutation on susceptibility to disease.IMPORTANCEThe Q223R leptin receptor mutation results in increased susceptibility of children and adults toE. histolytica, one of the leading causes of diarrhea morbidity and mortality in children of the developing world. Here we show that the mutation results in reduced neutrophil infiltration to the site of infection. This decreased infiltration is likely due to the mutation’s impact on neutrophil chemotaxis toward leptin, an inflammatory agent upregulated in the cecum after infection. The significance of this work thus extends beyond understandingE. histolyticasusceptibility by also providing insight into the potential impact of leptin on neutrophil function in other states of altered leptin signaling, which include both malnutrition and obesity.

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Entamoeba histolytica EhCP112 Dislocates and Degrades Claudin-1 and Claudin-2 at Tight Junctions of the Intestinal Epithelium

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2017.00372 ◽

2017 ◽

Vol 7 ◽

Cited By ~ 10

Author(s):

Patricia Cuellar ◽

Elizabeth Hernández-Nava ◽

Guillermina García-Rivera ◽

Bibiana Chávez-Munguía ◽

Michael Schnoor ◽

...

Keyword(s):

Tight Junctions ◽

Entamoeba Histolytica ◽

Intestinal Epithelium

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Further Observations on the Virus of Epizootic Diarrhea of Infant Mice. An Electron Microscopic Study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060568 ◽

1967 ◽

Vol 25 ◽

pp. 110-111

Author(s):

W. G. Banfield ◽

G. Kasnic ◽

J. H. Blackwell

Keyword(s):

Electron Microscope ◽

Infected Cell ◽

Microscopic Study ◽

Intestinal Epithelium ◽

Ultrastructural Study ◽

Osmium Tetroxide ◽

Lead Citrate ◽

Electron Microscopic ◽

Virus Particles ◽

Infected Cells

An ultrastructural study of the intestinal epithelium of mice infected with the agent of epizootic diarrhea of infant mice (EDIM virus) was first performed by Adams and Kraft. We have extended their observations and have found developmental forms of the virus and associated structures not reported by them.Three-day-old NLM strain mice were infected with EDIM virus and killed 48 to 168 hours later. Specimens of bowel were fixed in glutaraldehyde, post fixed in osmium tetroxide and embedded in epon. Sections were stained with uranyl magnesium acetate followed by lead citrate and examined in an updated RCA EMU-3F electron microscope.The cells containing virus particles (infected) are at the tips of the villi and occur throughout the intestine from duodenum through colon. All developmental forms of the virus are present from 48 to 168 hours after infection. Figure 1 is of cells without virus particles and figure 2 is of an infected cell. The nucleus and cytoplasm of the infected cells appear clearer than the cells without virus particles.

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Erythrophagocytosis by Entamoeba histolytica.- Ultrastructural Study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100094036 ◽

1972 ◽

Vol 30 ◽

pp. 156-157 ◽

Cited By ~ 1

Author(s):

Norberto Treviño ◽

Alfredo Feria-Velasco ◽

I. Ruiz de Chávez

Keyword(s):

Electron Microscopy ◽

Light Microscopy ◽

Entamoeba Histolytica ◽

Ultrastructural Study ◽

Saline Solution ◽

Physiological Saline ◽

Ultrastructural Level ◽

Hot Plate ◽

Physiological Saline Solution ◽

Axenic Conditions

Although erythrophagocytosis by various species of Entamoeba is a well known phenomenon this has not yet been studied in detail at the ultrastructural level. The present work deals with the description of the incorporation process of erythrocytes by trophozoites of E. histolytica. For this study, trophozoites of E. histolytica, HK-9:NIH strain cultured in axenic conditions and washed human erythrocytes were placed on a hot plate at 37°C in physiological saline solution. After 5 minutes, 2.5% glutarldehyde was added and the samples were processed according to conventional techniques for electron microscopy.Based upon light microscopy studies on living trophozoites in contact with erythrocytes, it seems that erythrophagocytosis only takes place in one pole of the parasite.

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Scanning electron microscopy of erythrophagocytosis by Entamoeba histolytica trophozoites

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012480x ◽

1992 ◽

Vol 50 (1) ◽

pp. 880-881

Author(s):

Victor Tsutsumi ◽

Adolfo Martinez-Palomo ◽

Kyuichi Tanikawa

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Red Blood Cells ◽

Entamoeba Histolytica ◽

Causative Agent ◽

Blood Cells ◽

Protozoan Parasite ◽

Complex Phenomenon ◽

Great Capacity ◽

Scanning Electron

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis in man. The trophozoite or motile form is a highly dynamic and pleomorphic cell with a great capacity to destroy tissues. Moreover, the parasite has the singular ability to phagocytize a variety of different live or death cells. Phagocytosis of red blood cells by E. histolytica trophozoites is a complex phenomenon related with amebic pathogenicity and nutrition.

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