Sustained immune activation is associated with susceptibility to the amphibian chytrid fungus

The disease chytridiomycosis caused by the fungusBdhas devastated amphibian populations worldwide. Functional genomic contributions to host susceptibility remain enigmatic and vary between species and populations. We conducted experimentalBdinfections inRana yavapaiensis, a species with intraspecific variation in chytridiomycosis susceptibility, to assess the skin and spleen transcriptomic response to infection over time. We predicted that increased immune gene expression would be associated with a positive disease outcome, but we instead found that surviving frogs had significantly reduced immune gene expression compared to susceptible frogs and to uninfected controls. MHC class II beta gene expression was also significantly higher in susceptible frogs compared to surviving frogs. Furthermore, susceptible frogs expressed a significantly larger number of distinct class II beta alleles, demonstrating a negative correlation between class II beta expression, functional diversity, and survival. Expression of the MHC class II beta locus previously associated withBddisease outcomes was a significant predictor ofBdinfection intensity at early infection stages but not at late infection stages, suggesting initial MHC-linked immune processes are important for ultimate disease outcomes. We infer through disease association and phylogenetic analysis that certain MHC variants are linked to the immune expression that was negatively associated with survival, and we hypothesize that frogs that did not express these alleles could better survive infections. Our study finds that MHC expression at early and late infection stages predictsBdinfection intensity, and suggests that generating a sustained immune response againstBdmay be counterproductive for surviving chytridiomycosis in this partially susceptible species.