A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children
Open Access
- 1 March 2011
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 121 (3), 1191-1198
- https://doi.org/10.1172/jci45294
Abstract
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.Keywords
This publication has 39 references indexed in Scilit:
- Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolyticaMucosal Immunology, 2010
- Functional Consequences of the Human Leptin Receptor (LEPR) Q223R TransversionObesity, 2009
- Genetics of gene expression and its effect on diseaseNature, 2008
- Maternal and child undernutrition: global and regional exposures and health consequencesThe Lancet, 2008
- Leptin promotes cell survival and activates Jurkat T lymphocytes by stimulation of mitogen-activated protein kinaseClinical and Experimental Immunology, 2008
- Entamoeba histolytica Phagocytosis of Human Erythrocytes Involves PATMK, a Member of the Transmembrane Kinase FamilyPLoS Pathogens, 2008
- Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin ReceptorNew England Journal of Medicine, 2007
- Adipocytokines: mediators linking adipose tissue, inflammation and immunityNature Reviews Immunology, 2006
- Towards a pro-inflammatory and immunomodulatory emerging role of leptinRheumatology, 2006
- The International HapMap ProjectNature, 2003