The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses in Wing Tissue of Hibernating Little Brown Myotis

PLoS Pathog. 2015 Oct 1;11(10):e1005168. doi: 10.1371/journal.ppat.1005168. eCollection 2015 Oct.


White-nose syndrome (WNS) in North American bats is caused by an invasive cutaneous infection by the psychrophilic fungus Pseudogymnoascus destructans (Pd). We compared transcriptome-wide changes in gene expression using RNA-Seq on wing skin tissue from hibernating little brown myotis (Myotis lucifugus) with WNS to bats without Pd exposure. We found that WNS caused significant changes in gene expression in hibernating bats including pathways involved in inflammation, wound healing, and metabolism. Local acute inflammatory responses were initiated by fungal invasion. Gene expression was increased for inflammatory cytokines, including interleukins (IL) IL-1β, IL-6, IL-17C, IL-20, IL-23A, IL-24, and G-CSF and chemokines, such as Ccl2 and Ccl20. This pattern of gene expression changes demonstrates that WNS is accompanied by an innate anti-fungal host response similar to that caused by cutaneous Candida albicans infections. However, despite the apparent production of appropriate chemokines, immune cells such as neutrophils and T cells do not appear to be recruited. We observed upregulation of acute inflammatory genes, including prostaglandin G/H synthase 2 (cyclooxygenase-2), that generate eicosanoids and other nociception mediators. We also observed differences in Pd gene expression that suggest host-pathogen interactions that might determine WNS progression. We identified several classes of potential virulence factors that are expressed in Pd during WNS, including secreted proteases that may mediate tissue invasion. These results demonstrate that hibernation does not prevent a local inflammatory response to Pd infection but that recruitment of leukocytes to the site of infection does not occur. The putative virulence factors may provide novel targets for treatment or prevention of WNS. These observations support a dual role for inflammation during WNS; inflammatory responses provide protection but excessive inflammation may contribute to mortality, either by affecting torpor behavior or causing damage upon emergence in the spring.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Ascomycota / pathogenicity
  • Chiroptera / genetics*
  • Chiroptera / immunology*
  • Chiroptera / microbiology*
  • Hibernation / immunology
  • High-Throughput Nucleotide Sequencing
  • Mycoses / genetics
  • Mycoses / immunology
  • Mycoses / veterinary*
  • Syndrome
  • Transcriptome
  • Virulence Factors / immunology
  • Wings, Animal / immunology


  • Virulence Factors

Grant support

This work was supported by the United States Fish and Wildlife Service grants F12AP01210 to DMR, F14AP00739 to DMR and KAF, and also the Woodtiger Fund to DMR and KAF and Bucknell University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.