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

Guo, Xiang; Roberts, Michelle; Becker, S.; Podd, Bradley S.; Zhang, Yiying; Chua, Streamson C.; Myers, Martin G.; Duggal, Priya; Houpt, Eric R.; Petri, William A.

doi:10.1038/mi.2010.76

Cited by 102 publications

(100 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a loss of resistance to amebiasis was seen in mice with specific deletion of the leptin receptor in the intestinal epithelium. In addition both leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice had increased susceptibility to amebiasis (33). These findings, together with the data presented here showing increased epithelial damage in Q223R mice, indicate that antiapoptotic leptin signaling at the intestinal epithelium may be required for resistance to amebiasis.…”

Section: Figuresupporting

confidence: 65%

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children

et al. 2011

View full text Add to dashboard Cite

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.

show abstract

Section: Figuresupporting

confidence: 65%

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared to children homozygous for the ancestral glutamine allele (223Q) (17). This finding was recapitulated in mouse studies, which in addition localized the protective effect of leptin to the intestinal epithelium (27). Additionally, intraluminal leptin signaling has been demonstrated to mediate conditions associated with intestinal inflammation, such as inflammatory bowel disease (57).…”

supporting

confidence: 58%

Leptin Protects Host Cells from Entamoeba histolytica Cytotoxicity by a STAT3-Dependent Mechanism

et al. 2012

View full text Add to dashboard Cite

ABSTRACTThe adipocytokine leptin links nutritional status to immune function. Leptin signaling protects from amebiasis, but the molecular mechanism is not understood. We developed anin vitromodel of ameba-host cell interaction to test the hypothesis that leptin prevents ameba-induced apoptosis in host epithelial cells. We demonstrated that activation of mammalian leptin signaling increased cellular resistance to amebic cytotoxicity, including caspase-3 activation. Exogenous expression of the leptin receptor conferred resistance in susceptible cells, and leptin stimulation enhanced protection. A series of leptin receptor signaling mutants showed that resistance to amebic cytotoxicity was dependent on activation of STAT3 but not the Src homology-2 domain-containing tyrosine phosphatase (SHP-2) or STAT5. A common polymorphism in the leptin receptor (Q223R) that increases susceptibility to amebiasis in humans and mice was found to increase susceptibility to amebic cytotoxicity in single cells. The Q223R polymorphism also decreased leptin-dependent STAT3 activation by 21% relative to that of the wild-type (WT) receptor (P= 0.035), consistent with a central role of STAT3 signaling in protection. A subset of genes uniquely regulated by STAT3 in response to leptin was identified. Most notable were the TRIB1 and suppressor of cytokine signaling 3 (SOCS3) genes, which have opposing roles in the regulation of apoptosis. Overall apoptotic genes were highly enriched in this gene set (P< 1E−05), supporting the hypothesis that leptin regulation of host apoptotic genes via STAT3 is responsible for protection. This is the first demonstration of a mammalian signaling pathway that restricts amebic pathogenesis and represents an important advance in our mechanistic understanding of how leptin links nutrition and susceptibility to infection.

show abstract

“…The findings of the present study might be related to role of leptin as a hormone in the gut 42. Leptin has shown to prevent epithelial apoptosis and promoting tissue repair, which are required for mucosal defence against pathogens 43. Due to the study design, the complexity and the multiple roles of leptin in human metabolism, it is not possible to unravel the mechanisms or to determine the causality of the association.…”

Section: Discussionmentioning

confidence: 79%

Intestinal parasites: Associations with intestinal and systemic inflammation

Zavala

García

Camacho

et al. 2018

Parasite Immunology

View full text Add to dashboard Cite

SummaryThe aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school‐aged children with high rates of obesity. Plasma concentrations of C‐Reactive Protein (CRP), leptin, TNF‐α, IL‐6 and IL‐10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6‐10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite‐free children while adjusting for sex, age, mother's educational level and percentage of body fat. The prevalence of soil‐transmitted helminths and intestinal protozoa infections was 12% and 36%, respectively. Parasitic infection was not associated with CRP, IL‐6, IL‐10 or TNF‐α. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97‐17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85‐25.14) were more likely to have higher stool leucocytes than parasite‐free children. Children with multiple infections (aOR: 10.60, 95% CI: 2.85‐25.14) were more likely to have higher leptin concentrations than parasite‐free children. Intestinal parasitic infection was not associated with systemic inflammation, but was associated with intestinal inflammation. Having multiple infections were associated with higher leptin concentrations.

show abstract

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

Cited by 102 publications

References 63 publications

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children

Leptin Protects Host Cells from Entamoeba histolytica Cytotoxicity by a STAT3-Dependent Mechanism

Intestinal parasites: Associations with intestinal and systemic inflammation

Contact Info

Product

Resources

About