Testosterone Increases Susceptibility to Amebic Liver Abscess in Mice and Mediates Inhibition of IFNγ Secretion in Natural Killer T Cells
Open Access
- 12 February 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (2), e55694
- https://doi.org/10.1371/journal.pone.0055694
Abstract
Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4− NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease.Keywords
This publication has 58 references indexed in Scilit:
- Engagement of glycosylphosphatidylinositol-anchored proteins results in enhanced mouse and human invariant natural killer T cell responsesImmunology, 2010
- A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-α and MIP1-β, a Lack of IL-17, and a Th1-Bias in MalesPLOS ONE, 2010
- Antigen-Specific Cytotoxicity by Invariant NKT Cells In Vivo Is CD95/CD178-Dependent and Is Correlated with Antigenic PotencyThe Journal of Immunology, 2010
- EBV Promotes Human CD8+ NKT Cell DevelopmentPLoS Pathogens, 2010
- Sexual Inequality in TuberculosisPLoS Medicine, 2009
- Editorial: NKT cells: to suppress or not to suppress, that is the questionJournal of Leukocyte Biology, 2009
- Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver AbscessPLoS Pathogens, 2009
- Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell‐clonotypic monoclonal antibody, 6B11Immunology, 2007
- Peripheral blood IFN‐γ‐secreting Vα24+Vβ11+ NKT cell numbers are decreased in cancer patients independent of tumor type or tumor loadInternational Journal of Cancer, 2005
- Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malariaLife Sciences, 1997