Response to Infections

I recall many years ago a colleague telling me his wife just delivered a very premature infant and stating he was grateful this child was female, stating she has a better chance of surviving due to her sex (she did survive and is thriving today). In addition, I have frequently used the Patient Outcomes Research Team score since its publication in 1997 to assess the status of patients with community-acquired pneumonia acknowledging the decrease of 10 points for severity score if the patient is female.1 These are just a couple personal acknowledgements that females having better outcomes than males for many infectious diseases.2 In this issue, Johnson et al provide an excellent review of various factors that affect response to infections and include evidence as to the difference of immunity based on sex.3 The review assesses many factors in addition to immunological differences and also includes anatomical, physiological, societal, and behavioral differences. IMMUNOLOGICAL DIFFERENCES Johnson et al point out that immunological differences influenced by genetic and endocrine differences play a significant role in response to infection. Differences in the chromosome (XX vs XY) have an effect on outcome of infections as the X chromosome contains more genes implicated in the immune response. This second X chromosome bestows a more vigorous humoral response both to infection and vaccination. As is discussed by Johnson et al, among the genes expressed by the X chromosome include those that promote development of T cells and toll-like receptors, which influences response to pathogens. In addition, the extra X chromosome protects females from the sex-linked conditions that occur in men. PREGNANCY Of note, the immune response of women does change during pregnancy as pointed out in the review; this is predominately to protect and not reject the fetus. Immunity shifts to humoral rather than cell mediated responses. This has been regarded by some as an evolutionary aspect, protecting women and the fetus during pregnancy and enhancing the mother's survival throughout the child-rearing years. This concept has also been observed in other species including insects, lizards, birds, and mammals. On the other hand, the benefit of increased immune responses decline as women age and especially after menopause.2 The heightened immune response of women does come with a down side as the risk of immune-mediated diseases is increased. Diseases more common in women include multiple sclerosis, rheumatoid arthritis, lupus, Sjogren's syndrome, and Graves disease. MICROBIOME DIFFERENCES The review by Johnson et al also describe a difference in the microbiomes of women and men, which are primarily shaped by the male (eg, testosterone) and female (eg, estrogen and progesterone) hormones. Disruption of these can affect susceptibility to infection. HORMONAL DIFFERENCES Hormonal differences between males and females also affect response to infection. Women benefit from estrogen, progesterone, and prolactin, which promote a balanced innate immune status. Testosterone is associated with a lessened response to infecton.4 The review provides many clinical scenarios, which are very helpful to illustrate the impact of the differences in immune response to infection and vaccines. The authors conclude by acknowledging these differences in responses to infection are “worthy of consideration in order to provide effective care of all patients,” a recommendation with which I certainly agree.