UNC Libraries · 2020 · 24 citations · 0 references
Life SciencesEndocrinologyImmunologyImmunizationImmunoregulationPsychoneuroimmunologyAndrogen PhysiologyEndocrine Regulation Of ImmunityImmune Response To VaccinationSex DifferencesTesticular FunctionVaccinationAndrogen ImmunomodulationImmunosuppressive FunctionSeasonal Influenza VaccinationSeasonal Influenza VaccinesSex Differences In SusceptibilitySex Hormone InfluencesSex-based Differences In Susceptibility
Sex differences in immune responses to infections and vaccination are pronounced, with females showing higher antibody responses, yet the underlying mechanisms remain largely unknown. The study aims to generate hypotheses linking sex-based immune differences to mechanisms affecting antibody responses to influenza vaccination. A systems immunology analysis identified a testosterone‑regulated lipid‑metabolism gene cluster that correlates with stronger antibody‑neutralizing responses in females, while males with high testosterone and related gene expression exhibit weaker responses.
Significance There are marked differences between the sexes in their immune response to infections and vaccination, with females often having significantly higher responses. However, the mechanisms underlying these differences are largely not understood. Using a systems immunology approach, we have identified a cluster of genes involved in lipid metabolism and likely modulated by testosterone that correlates with the higher antibody-neutralizing response to influenza vaccination observed in females. Moreover, males with the highest testosterone levels and expression of related gene signatures exhibited the lowest antibody responses to influenza vaccination. This study generates a number of hypotheses on the sex differences observed in the human immune system and their relationship to mechanisms involved in the antibody response to vaccination.