tetano
Editor, Senior Moderator
J Virol. 2017 Feb 8. pii: JVI.02160-16. doi: 10.1128/JVI.02160-16. [Epub ahead of print]
[h=1]Progesterone-based contraceptives reduce adaptive immune responses and protection against sequential influenza A virus infections.[/h] Hall OJ[SUP]1[/SUP], Nachbagauer R[SUP]2[/SUP], Vermillion MS[SUP]1,[/SUP][SUP]3[/SUP], Fink AL[SUP]1[/SUP], Phuong V[SUP]1[/SUP], Krammer F[SUP]2[/SUP], Klein SL[SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza A virus (IAV), are rarely evaluated. To evaluate their impact on immune responses to sequential IAV infections, adult female mice were treated with placebo or one of two progestins, P4 or levonorgestrel (LNG), and infected with mouse adapted (ma) H1N1 virus. Treatment with P4 or LNG reduced morbidity, but had no effect on pulmonary virus titers, during primary H1N1 infection as compared to placebo treatment. In serum and bronchoalveolar lavage fluid, total anti-IAV IgG and IgA titers and virus neutralizing antibody titers, but not hemagglutinin stalk antibody titers, were lower in progestin-treated mice as compared with placebo-treated mice. Females were challenged six weeks later with either a maH1N1 drift variant (maH1N1dv) or maH3N2 IAV. Protection following infection with the maH1N1dv was similar among all groups. In contrast, following challenge with maH3N2, progestin treatment reduced survival as well as numbers and activity of H1N1- and H3N2-specific memory CD8+ T cells, including tissue resident cells, compared with placebo treatment. In contrast to primary IAV infection, progestin treatment increased neutralizing and IgG antibody titers against both challenge viruses compared with placebo treatment. While the immunomodulatory properties of progestins protected na?ve females against severe outcome from IAV infection, it made them more susceptible to secondary challenge with a heterologous IAV, despite improving their antibody responses against a secondary IAV infection. Taken together, the immunomodulatory effects of progestins differentially regulate the outcome of infection depending on exposure history.IMPORTANCE The impact of hormone-based contraceptives on the outcome of infectious diseases outside of the reproductive tract is rarely considered. Using a mouse model, we have made the novel observation that treatment with either progesterone or a synthetic analog found in hormonal contraceptives, levonorgestrel, impacts sequential influenza A virus infection, by modulating antibody responses and decreasing memory CD8+ T cells. Progestins reduced antibody responses during primary H1N1 virus infection, but increased antibody titers following a sequential infection with either a H1N1 drift variant or a H3N2 virus. Following challenge with a H3N2 virus, female mice treated with progestins experienced greater mortality with increased pulmonary inflammation and reduced numbers and activity of CD8+ T cell. This study suggests that progestins significantly affect adaptive immune responses to influenza A virus infection, with their effect on influence outcome depending on exposure history.
Copyright ? 2017 American Society for Microbiology.
PMID: 28179523 DOI: 10.1128/JVI.02160-16
[PubMed - as supplied by publisher]
[h=1]Progesterone-based contraceptives reduce adaptive immune responses and protection against sequential influenza A virus infections.[/h] Hall OJ[SUP]1[/SUP], Nachbagauer R[SUP]2[/SUP], Vermillion MS[SUP]1,[/SUP][SUP]3[/SUP], Fink AL[SUP]1[/SUP], Phuong V[SUP]1[/SUP], Krammer F[SUP]2[/SUP], Klein SL[SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza A virus (IAV), are rarely evaluated. To evaluate their impact on immune responses to sequential IAV infections, adult female mice were treated with placebo or one of two progestins, P4 or levonorgestrel (LNG), and infected with mouse adapted (ma) H1N1 virus. Treatment with P4 or LNG reduced morbidity, but had no effect on pulmonary virus titers, during primary H1N1 infection as compared to placebo treatment. In serum and bronchoalveolar lavage fluid, total anti-IAV IgG and IgA titers and virus neutralizing antibody titers, but not hemagglutinin stalk antibody titers, were lower in progestin-treated mice as compared with placebo-treated mice. Females were challenged six weeks later with either a maH1N1 drift variant (maH1N1dv) or maH3N2 IAV. Protection following infection with the maH1N1dv was similar among all groups. In contrast, following challenge with maH3N2, progestin treatment reduced survival as well as numbers and activity of H1N1- and H3N2-specific memory CD8+ T cells, including tissue resident cells, compared with placebo treatment. In contrast to primary IAV infection, progestin treatment increased neutralizing and IgG antibody titers against both challenge viruses compared with placebo treatment. While the immunomodulatory properties of progestins protected na?ve females against severe outcome from IAV infection, it made them more susceptible to secondary challenge with a heterologous IAV, despite improving their antibody responses against a secondary IAV infection. Taken together, the immunomodulatory effects of progestins differentially regulate the outcome of infection depending on exposure history.IMPORTANCE The impact of hormone-based contraceptives on the outcome of infectious diseases outside of the reproductive tract is rarely considered. Using a mouse model, we have made the novel observation that treatment with either progesterone or a synthetic analog found in hormonal contraceptives, levonorgestrel, impacts sequential influenza A virus infection, by modulating antibody responses and decreasing memory CD8+ T cells. Progestins reduced antibody responses during primary H1N1 virus infection, but increased antibody titers following a sequential infection with either a H1N1 drift variant or a H3N2 virus. Following challenge with a H3N2 virus, female mice treated with progestins experienced greater mortality with increased pulmonary inflammation and reduced numbers and activity of CD8+ T cell. This study suggests that progestins significantly affect adaptive immune responses to influenza A virus infection, with their effect on influence outcome depending on exposure history.
Copyright ? 2017 American Society for Microbiology.
PMID: 28179523 DOI: 10.1128/JVI.02160-16
[PubMed - as supplied by publisher]