The role of sex hormones in the development of Th2 immunity in a gender-biased model of Trichuris muris infection.
Trichuris muris infection is an ideal model for defining T-cell-driven immunity, and also provides essential insights that may impact on potential helminth therapies currently in development. Conflicting host variables determine the efficiency of such treatments and we have identified host-derived sex steroid hormones as key factors in the development of immunity. The female-associated hormone 17-beta estradiol (E2) significantly enhanced the generation of a Th2 response in vitro; however, this stimulatory effect was found to be dispensable for the generation of immunity to Trichuris in the gender-biased IL-4KO mouse model. In contrast, the male-associated hormone dihydrotestosterone significantly inhibited the T-cell stimulatory capacity of DC and directly suppressed the immune response of male IL-4KO mice, with worm expulsion restored following castration. This finding was associated with dramatically reduced IL-18 mRNA expression suggesting androgens may act via this cytokine to suppress Th2 immunity to Trichuris. This study has critical implications for the development and efficacy of potential helminth therapeutics and identifies host gender - specifically sex hormones - as important factors in the development of Th2 immunity in susceptible and immunocompromised mice.
Hepworth
Matthew R
MR
Faculty of Life Sciences, University of Manchester, Manchester, England, UK.
Hardman
Matthew J
MJ
Grencis
Richard K
RK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D009919:Orchiectomy; D010052:Ovariectomy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014257:Trichuriasis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014258:Trichuris / Q000254:growth & development / Q000276:immunology*
D012739:Gonadal Steroid Hormones; D020382:Interleukin-18; D013196:Dihydrotestosterone; D015847:Interleukin-4; D004958:Estradiol