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

Abstract

The disease chytridiomycosis caused by the fungus Bd has devastated amphibian populations worldwide. Functional genomic contributions to host susceptibility remain enigmatic and vary between species and populations. We conducted experimental Bd infections in Rana 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 IIβ gene expression was also significantly higher in susceptible frogs compared to surviving frogs. Furthermore, susceptible frogs expressed a significantly larger number of distinct class IIβ alleles, demonstrating a negative correlation between class IIβ expression, functional diversity, and survival. Expression of the MHC class IIβ locus previously associated with Bd disease outcomes was a significant predictor of Bd infection 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 predicts Bd infection intensity, and suggests that generating a sustained immune response against Bd may be counterproductive for surviving chytridiomycosis in this partially susceptible species.

Whole exome sequencing identifies the potential for genetic rescue in iconic and critically endangered Panamanian harlequin frogs

“…The role of the immune system in the host‐ Bd relationship varies widely among amphibian species. For example, transcriptomic studies have found that some susceptible species show an increase in the expression of immune genes when exposed to Bd (Ellison et al., 2014; Savage et al., 2020), while others have suppressed or undetectable immune responses (Ellison et al, 2014; Rosenblum et al., 2012). Other studies have shown that Bd inhibits lymphocytes, indicating that it actively suppresses host acquired immunity (Fites et al., 2013).…”

“…The presence of previously studied, immunologically relevant genes in our candidate list supports previous work showing that immune system processes are important for Bd tolerance or resistance in these species (Ellison et al., 2014). Intriguingly, a growing number of studies indicate that an overactivation of the immune system may be linked to Bd susceptibility for some species (Ellison et al., 2014; Savage et al., 2020). We propose that toll‐like receptor genes, and others that interact with this immune pathway such as LYST, may be key players in mounting an appropriate immune response to Bd .…”

Panzootic chytrid fungus exploits diverse amphibian host environments through plastic infection strategies

“…Chytridiomycosis threatens amphibian populations worldwide, however, disease risk varies greatly depending on a myriad of factors, including Bd lineage (12,13,16,24). While several studies have characterized the infection response of different amphibian species (21,(28)(29)(30)(31)(32)(33)(34)(35), our work contributes to identify Bd's functional machinery driving invasion and disease dynamics in a wide amphibian host range. In this study, we provide a framework to integrate available transcriptome data to further explore pathogen functional genomics during host-pathogen interactions.…”

Immunological Aspects of Chytridiomycosis

“…This is known as immunopathology, i.e., excessive damage caused by the immune response. Transcriptomics studies on chytridiomycosis have revealed that animals eventually succumbing to infection demonstrate evidence of such immunopathology [83,126,141,170,178]. This immunopathology is characterised by much higher numbers and variety of dysregulated immune genes being expressed in the final stages of infection compared to less susceptible animals and unexposed control animals.…”