Males and Females Are Not Equal When it Comes to Infection

One of the "iron laws" of the mammal kingdom is that females tend to live longer than males, all other things being equal. Indeed, among humans, it is clear that any society experiencing higher death rates for girls/women than for boys/men is one in which females are heavily discriminated against. We know that the female biological advantage begins in utero and extends to the oldest age. But what are the mechanisms? We may never know the full answer, although the biggest bets relate to hormones, since they are the clearest way in which males differ from females. An article out today in Nature.com takes this issue on, showing that infection rates are different by sex, suggesting that there are differences in the immune system.

The immune systems of men and women respond very differently to infection — and scientists are taking notice. Research presented last week at a microbiology meeting in Boston, Massachusetts, suggests that the split could influence the design of vaccination programmes and lead to more targeted treatment of illness.

Now, scientists are beginning to tease out some precise mechanisms. At the meeting, infectious-disease researcher Katie Flanagan at the University of Tasmania in Australia reported on a tuberculosis vaccine given to Gambian infants. She found that the vaccine suppressed production of an anti-inflammatory protein in girls, but not boys. This boosted the girls’ immune responses, and may have made the vaccine more effective.

Hormones also play a part. Oestrogen can activate the cells involved in antiviral responses, and testosterone suppresses inflammation. Treating nasal cells with oestrogen-like compounds before exposing them to the influenza virus has revealed further clues, says Sabra Klein, an endocrinologist at Johns Hopkins University in Baltimore, Maryland. Only the cells from females responded to the hormones and fought off the virus (J. Peretz et al. Am. J. Physiol. http://doi.org/bj5w; 2016).

One of the more intriguing studies mentioned is one that compares immune responses before and after sex-change operations.

A study set to begin later this year could help to tease apart the relative influence of genes and hormones on infection. Altfeld and his colleagues will look at 40 adults going through sex-change operations. If female hormones are responsible, the transgender women in the study should begin mounting stronger immune reactions to infections and develop more autoimmune problems than the transgender men.

These kinds of results, when combined with advances in regenerative medicine, are among the reasons why we can expect to see continued increases in life expectancy among humans.