Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection
JournalEmerging Microbes and Infections
PublisherTaylor and Francis Ltd.
MetadataShow full item record
AbstractEstradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections. Copyright 2019 The Author(s).
SponsorsThis work was supported by the FDA Office of Women's Health (OWH) fund (to Xie H). CL Finch and A. Zhang were on the FDA OWH sponsored ORISE Research Fellowship via the administration of the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and FDA/CBER.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85070068799&doi=10.1080%2f22221751.2019.1648184&partnerID=40&md5=d0f52f74121aa78e36b6338cb671d076; http://hdl.handle.net/10713/10349