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.

Imported Amoebic Liver Abscess in France

“…For instance, analysis of pyogenic liver abscesses in Denmark over a 30-year period, showed that men were more likely to be affected [16]. This finding is also consistent with the animal model, as Lotter et al demonstrated that male mice developed larger ALA than female mice [17], [18]. Hormonal factors have been suggested to explain this difference [15].…”

“…Indeed in humans, Snow et al showed that female serum was more effective in killing E. histolytica trophozoïtes than a male one, thanks to the complement system [20]. In the animal model, female mice recovered more rapidly than their male counterparts due to a higher production of Interferon-γ [17] secreted by Natural Killer T Cells [18].The absence of association with HIV infection and ALA size in our study, is contradictory to this immunological hypothesis, but can be attributed once again to the low number of subjects. In a study involving more than 2000 ALA cases from an endemic region, Blessmann et al showed a peak incidence at 40–49 of age as in our cohort [8].…”

Burden of Liver Abscess and Survival Risk Score in Thailand: A Population-Based Study

“…It has also been reported that testosterone influences susceptibility to ALA in a mouse model of the disease. 11 Our data demonstrate different geographic distributions of endemic liver abscess. It is known that the northeastern part of Thailand has a very high incidence of B. pseudomallei.…”

Neuroendocrine control of photoperiodic changes in immune function

“…Estrogens can reduce recruitment of neutrophils in humans and experimental animals (Pacifici, 2008; Sheh et al ., 2011; Shih et al ., 2011). Testosterone inhibits the secretion of interferon-γ (IFN-γ) from natural killer cells increasing pathogen proliferation (Lotter et al ., 2013). Estrogen deficiency promotes the production of tumor necrosis factor-α (TNF-α) production from T cells (Pacifici, 2008).…”