Most people will have heard the term? Man flu? Refers to men’s perceived tendency to exaggerate the severity of a cold or a similar minor ailment. But this is more than just a male thing; sex differences in immune responses to infections have long been observed. Men are more susceptible to some pathogens, suffer more severe disease symptoms, and are at greater risk of developing autoimmune disorders such as rheumatoid arthritis and lupus.
The causes of these gender differences in immune responses are complex and relate to genetic, environmental, and hormonal factors that can change throughout the lifetime of humans. These include variations in the concentrations of sex hormones, such as testosterone and progesterone, produced by the gonads of both males and females. A variety of other genes and regulators also modulate these. One is CD200, a protein essential for inhibiting TLR-7 responses (TLR stands for toll-like receptor-7), which is involved in antiviral immunity, inflammatory reactions, and other noninfectious diseases.
Studies of viral infections, such as the 2003 SARS epidemic and the 2013-2014 MERS coronavirus pandemic, have shown that, in general, women are more affected by these pathogens than men. While this difference is partially explained by the fact that women carry two X chromosomes, which silences many genes and reduces their expression, other reasons for these differences are more difficult to explain.
But researchers are starting to understand how biological sex can alter immune responses to other diseases, too. For example, the estrogen hormone, which enhances immune responses, is high during pregnancy and in the years leading up to it. It is also a significant factor in autoimmune conditions like lupus, affecting more women than men.
Other research suggests that differences in innate immune responses are due to variations in the size of certain brain parts. A 2016 study found that the preoptic area, which helps regulate fevers during infection, is more significant in men than women. This might be one reason men’s symptoms feel more severe than women’s when they are sick.
Ultimately, this research is helping scientists to define how and why men’s and women’s immune responses differ and may contribute to understanding why some people are more successful than others with immunotherapies such as checkpoint inhibitors. Whether or not the COVID-19 outbreak will help to bring these questions into sharper focus remains to be seen. But the current situation is shedding light on a truth about how human immune systems work that has long been hidden from view. Men suffer from weaker immune systems than women and are more susceptible to some infectious diseases, even when taking the same precautions against them.