Abstract
Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that genes (hereafter 'markers') can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response.
Highlights
Natural variability cannot be fully reproduced in the laboratory, which has led to a recent effort to characterise the immune response in wild populations of mice or other rodents
Given that we study a mixed population of cells, variation in the responses we measure could result from both the relative proportion and activation state of different cell types in different individual animals
We describe three main categories of response to stimulation: (i) uncorrelated response, (ii) constant response and (iii) baseline-dependent response. Across these three categories, which show high individual variability in response. We suggest that such categorisation is useful in organising natural variation in response, since little is known about which components of immune pathways are responsible for natural variability in immune response, or about the nature of such variability
Summary
Given that we study a mixed population of cells (splenocytes), variation in the responses we measure could result from both the relative proportion and activation state of different cell types in different individual animals Each of these things could, potentially, be driven independently by different causal drivers in individual animals and, both could affect the strength and phenotypic direction of any response. The ability of an immune response to effect protection against infection, for example, will be supported by a variety of non-immune functions, that will be activated following stimulation by an agonist, and vary to a greater or lesser extent among individuals within a natural population. By identifying the components (whether conventionally immunological or not) that are likely to be responsible for natural variability in immune response, and by describing the nature of their variability, we are laying the groundwork for exploring the processes, whether genetic or environmental, which drive individual variation in immune response
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