Seminars in Immunopathology

, Volume 41, Issue 2, pp 189–194 | Cite as

Sex and sex steroids impact influenza pathogenesis across the life course

  • Landon G. vom Steeg
  • Sabra L. KleinEmail author


Males and females differ in the outcome of influenza A virus (IAV) infections, which depends significantly on age. During a typical seasonal influenza epidemic, young children (< 10 years of age) and aged adults (65+ years of age) are at greatest risk for severe disease, and among these age groups, males tend to suffer a worse outcome from IAV infection than females. Following infection with either pandemic or outbreak strains of IAVs, females of reproductive ages (i.e., 15–49 years of age) experience a worse outcome than their male counterparts. Among females of reproductive ages, pregnancy is one factor linked to an increased risk of severe outcome of influenza, although it is not the sole factor explaining the female-preponderance of severe disease. Small animal models of influenza virus infection illustrate that inflammatory immune responses and repair of damaged tissue following IAV infection also differ between the sexes and impact the outcome of infection. There also is growing evidence that sex steroid hormones, including estrogens, progesterone, and testosterone, directly impact immune responses during IAV infection to alter outcomes. Greater consideration of the combined effects of sex and age as biological variables in epidemiological, clinical, and animal studies of influenza pathogenesis is needed.


Estrogen Gender Immunopathology Pandemic Progesterone Testosterone 



The writing of this review was supported by the NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N272201400007C (SLK).


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular Microbiology and ImmunologyThe Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA

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