title: Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNγ secretion in natural killer T cells.
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.
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. lotter@bni-hamburg.de
authors: Hannelore
authors: H
authors: Lotter
authors: Elena
authors: E
authors: Helk
authors: Hannah
authors: H
authors: Bernin
authors: Thomas
authors: T
authors: Jacobs
authors: Cornelia
authors: C
authors: Prehn
authors: Jerzy
authors: J
authors: Adamski
authors: Nestor
authors: N
authors: González-Roldán
authors: Otto
authors: O
authors: Holst
authors: Egbert
authors: E
authors: Tannich
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D004198:Disease Susceptibility; D004748:Entamoeba histolytica / Q000737:chemistry / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D008101:Liver Abscess, Amebic / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D013739:Testosterone; D007371:Interferon-gamma