Pleiotropy links host axes of defense against a pathogen

Abstract

Organisms face ubiquitous threats from pathogens, and in response hosts have evolved a cascade of defenses to avoid, resist, or tolerate infection. While these stepwise defenses may act independently, they can be pleiotropically linked via shared molecular mechanisms, regulation, and crosstalk. Here, we tested the extent to which pleiotropy shapes multiple axes of defense using knockouts of 16 single genes involved in innate immunity of Caenorhabditis elegans against the opportunistic bacterial pathogen Pseudomonas aeruginosa. Host genotype had variable effects on components of host defense. Traits such as infection-induced mortality and body size varied frequently across host genotypes, while behavioral avoidance, bacterial uptake, and susceptibility to bacterial colonization varied less frequently. Broadly, pleiotropy between defenses was common, driving patterns of variation that linked several traits together. However, important components of defense like mortality, avoidance, and susceptibility to colonization were more independent from one another. Our results show that pleiotropy between defenses can be common, highlighting the importance of moving beyond single phenotypes to understand multiple dimensions of host-pathogen interactions.