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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

Global transcriptional analysis of WNS-affected and unaffected bats by RNA-Seq.Centered log2 fold changes are shown for the 100 most significant differentially expressed identified genes. Adjusted p values ranged from 3.3x10-5 to 2.8x10-18. The heatmap of TMM-normalized FPKM expression estimates is centered and log2 scaled from a minimum of -4.8 to a maximum of 4.8. Transcripts were identified by BLAST alignment to the SwissProt database.
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ppat.1005168.g002: Global transcriptional analysis of WNS-affected and unaffected bats by RNA-Seq.Centered log2 fold changes are shown for the 100 most significant differentially expressed identified genes. Adjusted p values ranged from 3.3x10-5 to 2.8x10-18. The heatmap of TMM-normalized FPKM expression estimates is centered and log2 scaled from a minimum of -4.8 to a maximum of 4.8. Transcripts were identified by BLAST alignment to the SwissProt database.

Mentions: Expression levels for the Swissprot-identified transcript clusters with the 100 lowest adjusted p values are shown in Fig 2 (see S4 Table for all results). Some of the differentially expressed genes with putative functions that were predicted to associate with host responses to a fungal pathogen are listed in Table 2. WNS caused dramatic changes in expression of genes involved in inflammation, immune responses, wound healing, metabolism, and oxidative stress, even though the bats were hibernating during the Pd infection. Most of these genes were upregulated in WNS-affected tissues, while a much smaller number of identified genes with putative functions in these categories were downregulated (Tables 2 and S4).


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)

Global transcriptional analysis of WNS-affected and unaffected bats by RNA-Seq.Centered log2 fold changes are shown for the 100 most significant differentially expressed identified genes. Adjusted p values ranged from 3.3x10-5 to 2.8x10-18. The heatmap of TMM-normalized FPKM expression estimates is centered and log2 scaled from a minimum of -4.8 to a maximum of 4.8. Transcripts were identified by BLAST alignment to the SwissProt database.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005168.g002: Global transcriptional analysis of WNS-affected and unaffected bats by RNA-Seq.Centered log2 fold changes are shown for the 100 most significant differentially expressed identified genes. Adjusted p values ranged from 3.3x10-5 to 2.8x10-18. The heatmap of TMM-normalized FPKM expression estimates is centered and log2 scaled from a minimum of -4.8 to a maximum of 4.8. Transcripts were identified by BLAST alignment to the SwissProt database.
Mentions: Expression levels for the Swissprot-identified transcript clusters with the 100 lowest adjusted p values are shown in Fig 2 (see S4 Table for all results). Some of the differentially expressed genes with putative functions that were predicted to associate with host responses to a fungal pathogen are listed in Table 2. WNS caused dramatic changes in expression of genes involved in inflammation, immune responses, wound healing, metabolism, and oxidative stress, even though the bats were hibernating during the Pd infection. Most of these genes were upregulated in WNS-affected tissues, while a much smaller number of identified genes with putative functions in these categories were downregulated (Tables 2 and S4).

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