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

Field KA, Johnson JS, Lilley TM, Reeder SM, Rogers EJ, Behr MJ, Reeder DM - PLoS Pathog. (2015)

Bottom Line: We found that WNS caused significant changes in gene expression in hibernating bats including pathways involved in inflammation, wound healing, and metabolism.However, despite the apparent production of appropriate chemokines, immune cells such as neutrophils and T cells do not appear to be recruited.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Bucknell University, Lewisburg, Pennsylvania, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Hierarchical clustering of gene expression in WNS-affected and unaffected bats.Hierarchical clustering of differentially expressed genes using Pearson correlation complete-linkage clustering. Scale shows Pearson correlation coefficient.
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ppat.1005168.g001: Hierarchical clustering of gene expression in WNS-affected and unaffected bats.Hierarchical clustering of differentially expressed genes using Pearson correlation complete-linkage clustering. Scale shows Pearson correlation coefficient.

Mentions: We compared host gene expression across all samples (S2 Dataset) using DESeq2 [67] to identify transcript clusters that were expressed at a minimum of 2-fold difference and significant at a false discovery rate (FDR) of 0.05 (S1 Fig). We found 1804 transcript clusters that were expressed at higher levels, and 1925 transcript clusters expressed at lower levels, in WNS-affected bat tissues (S4 Table). Hierarchical clustering (Fig 1) revealed that expression of these transcripts from all 5 bats without WNS was similar to each other. Gene expression in wing tissue from WNS-affected bats was different from unaffected bats and more similar to each other, as predicted. The normalized expression levels of the 3729 identified transcript clusters differentially expressed are listed in S4 Table.


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

Field KA, Johnson JS, Lilley TM, Reeder SM, Rogers EJ, Behr MJ, Reeder DM - PLoS Pathog. (2015)

Hierarchical clustering of gene expression in WNS-affected and unaffected bats.Hierarchical clustering of differentially expressed genes using Pearson correlation complete-linkage clustering. Scale shows Pearson correlation coefficient.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591128&req=5

ppat.1005168.g001: Hierarchical clustering of gene expression in WNS-affected and unaffected bats.Hierarchical clustering of differentially expressed genes using Pearson correlation complete-linkage clustering. Scale shows Pearson correlation coefficient.
Mentions: We compared host gene expression across all samples (S2 Dataset) using DESeq2 [67] to identify transcript clusters that were expressed at a minimum of 2-fold difference and significant at a false discovery rate (FDR) of 0.05 (S1 Fig). We found 1804 transcript clusters that were expressed at higher levels, and 1925 transcript clusters expressed at lower levels, in WNS-affected bat tissues (S4 Table). Hierarchical clustering (Fig 1) revealed that expression of these transcripts from all 5 bats without WNS was similar to each other. Gene expression in wing tissue from WNS-affected bats was different from unaffected bats and more similar to each other, as predicted. The normalized expression levels of the 3729 identified transcript clusters differentially expressed are listed in S4 Table.

Bottom Line: We found that WNS caused significant changes in gene expression in hibernating bats including pathways involved in inflammation, wound healing, and metabolism.However, despite the apparent production of appropriate chemokines, immune cells such as neutrophils and T cells do not appear to be recruited.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Bucknell University, Lewisburg, Pennsylvania, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus