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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

REVIGO treemap summarizing gene ontology biological process categories over-represented in WNS-affected tissues.GOrilla was used to identify Gene Ontology Biological Processes that were over-represented among transcripts more highly expressed in WNS-affected tissues at an FDR cutoff of 0.1 (S6 Table). Over-represented categories with p values of less than 0.001 (290 terms) were used to generate a treemap colored by functional category. The size of each rectangle is proportional to the p value for that category.
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ppat.1005168.g004: REVIGO treemap summarizing gene ontology biological process categories over-represented in WNS-affected tissues.GOrilla was used to identify Gene Ontology Biological Processes that were over-represented among transcripts more highly expressed in WNS-affected tissues at an FDR cutoff of 0.1 (S6 Table). Over-represented categories with p values of less than 0.001 (290 terms) were used to generate a treemap colored by functional category. The size of each rectangle is proportional to the p value for that category.

Mentions: We next examined the functional pathways that were most affected in little brown myotis infected with Pd. For this gene ontology analysis, DESeq2 results on transcript isoforms were used with a higher FDR threshold of 0.1, as is typical for this type of analysis. From WNS-affected bat tissue, 3104 upregulated transcripts were aligned with BLAST to the human Uniprot database. Homologs for these transcripts were identified and a list of 1937 unique Ensembl IDs associated with upregulated genes was generated (S6 Table). GOrilla [70] was used to determine significantly upregulated gene ontology categories from the Uniprot GO ID database (Table 3 and S7 Table) and REVIGO [71] was used to visualize biological processes that were significantly overrepresented in the WNS-affected transcriptome (Fig 4). The functional analysis revealed that Pd infection increases expression of genes involved in metabolism, defense responses, and other pathways (Table 3).


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)

REVIGO treemap summarizing gene ontology biological process categories over-represented in WNS-affected tissues.GOrilla was used to identify Gene Ontology Biological Processes that were over-represented among transcripts more highly expressed in WNS-affected tissues at an FDR cutoff of 0.1 (S6 Table). Over-represented categories with p values of less than 0.001 (290 terms) were used to generate a treemap colored by functional category. The size of each rectangle is proportional to the p value for that category.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005168.g004: REVIGO treemap summarizing gene ontology biological process categories over-represented in WNS-affected tissues.GOrilla was used to identify Gene Ontology Biological Processes that were over-represented among transcripts more highly expressed in WNS-affected tissues at an FDR cutoff of 0.1 (S6 Table). Over-represented categories with p values of less than 0.001 (290 terms) were used to generate a treemap colored by functional category. The size of each rectangle is proportional to the p value for that category.
Mentions: We next examined the functional pathways that were most affected in little brown myotis infected with Pd. For this gene ontology analysis, DESeq2 results on transcript isoforms were used with a higher FDR threshold of 0.1, as is typical for this type of analysis. From WNS-affected bat tissue, 3104 upregulated transcripts were aligned with BLAST to the human Uniprot database. Homologs for these transcripts were identified and a list of 1937 unique Ensembl IDs associated with upregulated genes was generated (S6 Table). GOrilla [70] was used to determine significantly upregulated gene ontology categories from the Uniprot GO ID database (Table 3 and S7 Table) and REVIGO [71] was used to visualize biological processes that were significantly overrepresented in the WNS-affected transcriptome (Fig 4). The functional analysis revealed that Pd infection increases expression of genes involved in metabolism, defense responses, and other pathways (Table 3).

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