We often use experiments in controlled laboratory infections to understand how parasites impact hosts. Laboratory studies have been crucial in identifying molecular details of infection and immunity.
However, we know that individuals vary in their susceptibility to infection. This variation has important impacts on how a disease spreads through a population and affects the efficacy of control programs. Some of this variation in susceptibility can be explained by genetics, but the environment also plays a key role. Abiotic (i.e. rainfall) and/or biotic (i.e. gut microbiota) environmental heterogeneity can also lead to differences in susceptibility of hosts. But because lab studies often control for environmental conditions, they offer limited abilities to study variation in host susceptibility. Incorporating this complexity into experiments is an important, albeit difficult exercise.
Leung and colleagues have recently published a paper in which they bridge the gap between laboratory and field studies of host susceptibility. They rewilded laboratory mice in a natural farm-like setting (i.e. country mouse; Figure 1). So called ‘Long term wild’ mice were introduced to the semi-natural enclosures before experimental infection with Trichuris muris (nematode parasite) whereas ‘short term wild’ mice were introduced 10 days after infection.
The authors measured infection susceptibility, gut microbiota, and immune responses of both the rewilded mice and a group of mice that never left the lab. They used the same inbred strain of mice of treatment groups, so they were able to control for the effects of host genetics on these outcomes.
Before the experiment began, they hypothesized that exposure of mice to a natural microbial environment should impact susceptibility of the hosts. They suspected that altered microbes would directly impact the hatching, growth and development of worms, but they could also indirectly impact worms through changes in gut.
After 3 weeks, the ‘wild’ mice had significantly higher amounts of worms than mice in the lab. Not enough time had passed to allow for any new transmission, so this was simply due to environmental effects. Additionally, the long term wild mice had heavier worms than their short term neighbours.
Moving to the country before infection resulted in a change in the bacteria inside a mouse’s gut. However mice that were only in the country for a week did not have a significantly different gut microbiota compared to lab mice. Alongside this shift in microbiota, the mice in the country had decreased Th2 and increased Th1 cytokines compared to lab mice. This suggests immune responses were changed by the environment as well.
This study is unique in its attempts to understand variation in host susceptibility to infection.