Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone.
Testosterone induces susceptibility to Plasmodium chabaudi malaria by imposing restrictions on those mechanisms which mediate resistance controlled by genes of the H-2 complex and the non-H-2 background in mice. This study investigated whether these restrictions are abolished after withdrawal of testosterone. Female mice of the inbred strain C57BL/10 were treated with 0.9 mg testosterone twice a week for 3 weeks and testosterone was then withdrawn for 12 weeks. The treatment raised plasma testosterone levels from 0.18 ng/ml to 3.79 ng/ml. After the testosterone treatment, these levels progressively dropped and reached 0.21 ng/ml by week 12 after testosterone withdrawal. Surprisingly, however, the testosterone-induced susceptibility still persisted. When mice were challenged on week 12 after testosterone withdrawal, P. chabaudi infections were still fatal in testosterone-treated mice, in contrast to self-healing infections in resistant, i.e. untreated, control mice. In addition, testosterone caused a persistent decrease in the levels of total IgG antibodies, especially IgG1 and IgG2b isotypes. In contrast, testosterone-induced changes in spleen cells, such as the reduction in number by 50%, the relative increase in CD8+ cells and the decrease in Ig+ cells, as well as the acquisition of the susceptible phenotype, were completely reversed on week 10 after testosterone withdrawal at the latest. Testosterone did not affect the production of the TH1-signalling cytokine interferon-gamma and the TH2-signalling cytokines interleukin (IL)-4 and IL-10 in response to P. chabaudi malaria. Together, our data indicated that the gene-controlled host resistance to P. chabaudi malaria is subject to superior hormonal imprinting: when once induced by testosterone, mechanisms which suppress resistance thus causing susceptibility persist independently of testosterone.
Benten
W P
WP
Division of Molecular Parasitology, Heinrich Heine University, Düsseldorf, Germany.
Ulrich
P
P
Kühn-Velten
W N
WN
Vohr
H W
HW
Wunderlich
F
F
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D013739:Testosterone; D007371:Interferon-gamma