Protective microbiomes can limit the evolution of host pathogen defense

Abstract

The evolution of host immunity occurs in the context of the microbiome, but little theory exists to predict how resistance against pathogens might be influenced by the need to tolerate and regulate commensal microbiota. We present a general model to explore the optimal investment in host immunity under conditions in which the host can, versus cannot easily distinguish among commensal versus pathogenic bacteria; and when commensal microbiota can, versus cannot protect the host against the impacts of pathogen infection. We find that a loss of immune vigilance associated with innate immunity over evolutionary time can occur due to the challenge of discriminating between pathogenic and other microbe species. Further, we find the greater the protective effect of microbiome species, acting either directly or via competition with a pathogen, or the higher the costs of immunity, the more likely the loss of immune vigilance is. Conversely, this effect can be reversed when pathogens increase host mortality. Generally, the magnitude of costs of immunity required to allow evolution of decreased immune vigilance are predicted to be lowest when microbiome and pathogen species most resemble each other (in terms of host recognition), and when immune effects on the pathogen are weak. Our model framework makes explicit the core trade-offs likely to shape the evolution of immunity in the context of microbiome / pathogen discrimination. We discuss how this informs interpretation of patterns and process in natural systems, including vulnerability to pathogen emergence.\n\nImpact SummaryEvidence for impacts of the microbiome on host health is accumulating. Despite this, little theory has been developed to delineate the evolutionary trajectories that might lead to observed host-microbiome associations. One particularly important theoretical gap is evaluating how the presence and effects of microbiome species modify selection pressure on immune system function. We develop a simple model of host fitness given both immune discrimination and microbiome and pathogen effects on survival, in the context of an interaction between the microbiome and pathogen species. We use this framework to predict when and to what degree the presence of microbiome species might lead to loss of immune vigilance. Positive microbiome effects can drive loss of immune vigilance, whether the microbiome acts directly on pathogen growth or indirectly by reducing the impacts of pathogens; and high costs of immunity will amplify this effect. Our results provide a first set of predictions regarding how immunity should evolve given the challenge of discriminating pathogen and microbiome species, and reveals the ways in which this might leave hosts vulnerable to novel pathogens.