Is there a sicker sex? Dose relationships modify male-female differences in infection prevalence

Abstract

Throughout the animal kingdom there are striking differences in the propensity of one sex or the other to become infected. However, attempts to generalise when we should expect males or females to emerge as the sicker sex have proven challenging. We argue that this is because our current understanding of sex differences in susceptibility is inherently limited, as most inferences have come from field studies (where exposure dose is difficult to quantify), or by measuring infection rates in vitro at a limited range of pathogen doses. Without considering how susceptibility changes across a range of pathogen doses (i.e., the dose-susceptibility relationship), we have likely underestimated the scope in which sex differences can arise, reducing our capacity to accurately characterise the sicker sex. Here, to expand our scope, we use the Daphnia magnia and Pasteuria ramosa system to measure infection prevalence across a fifteen thousandfold change in pathogen dose and quantify male and female differences through formal models of environmental transmission. Through this, we reveal that the expression of sex differences in susceptibility is entirely dose-dependent, with males more susceptible at low doses, and females more susceptible at high doses. The scope for male-female differences to emerge is therefore much greater than previously expected - extending to differences in absolute resistance, per-propagule infectivity risks, and the dose-specific behaviour of pathogens. Crucially, none of these components in isolation could define the sicker sex. If we wish to understand the broader patterns underlying whether males or females are the sicker sex, there is a need to apply this expanded scope across the animal kingdom. This will help us understand when and why a sicker sex emerges, and the implications for diseases in nature - where sex ratios and pathogen densities vary drastically.