Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility

Emily F. Mantilla Valdivieso; Elizabeth M. Ross; Ali Raza; Loan Nguyen; Ben J. Hayes; Nicholas N. Jonsson; Peter James; Ala E. Tabor

doi:10.1038/s41598-024-54577-w

Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility

Emily F. Mantilla Valdivieso, Elizabeth M. Ross^*, Ali Raza, Loan Nguyen, Ben J. Hayes, Nicholas N. Jonsson^*, Peter James, Ala E. Tabor^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-naïve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR < 0.05), of which 212 were the target of at least 1866 transcription factors (TFs) expressed in skin. Regulatory impact factor (RIF) analysis identified 158 significant TFs (P < 0.05) of which GRHL3, and DTX1 were also DEGs in the experiment. Gene term enrichment showed the significant TFs and DEGs were enriched in processes related to immune response and biological pathways related to host response to infectious diseases. Interferon Type 1-stimulated genes, including MX2, ISG15, MX1, OAS2 were upregulated in low host resistance steers after repeated tick challenge, suggesting dysregulated wound healing and chronic inflammatory skin processes contributing to host susceptibility to ticks. The present study provides an assessment of the bovine skin transcriptome before and after repeated tick challenge and shows that the up-regulation of pro-inflammatory genes is a prominent feature in the skin of tick-susceptible animals. In addition, the identification of transcription factors with high regulatory impact provides insights into the potentially meaningful gene–gene interactions involved in the variation of phenotypes of bovine host resistance to ticks.

Original language	English
Article number	4419
Journal	Scientific Reports
Volume	14
Issue number	1
Number of pages	14
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-024-54577-w
Publication status	Published - 2024
Externally published	Yes

Bibliographical note

Funding Information:
This research was funded by the Meat and Livestock Australia Donor Company (MDC) grant P.PSH.0798 supported by the Queensland Department of Agriculture & Fisheries entitled ‘Cattle tick and buffalo fly host genetics, susceptibility to buffalo fly lesions and biomarkers for resistance’. EFMV was supported by an Australian Government Research Training Program (RTP) Scholarship.

Funding Information:
The authors thank Tom Conolly, Alison Moore, Muhammad Noman Naseem and Muhammad Karman for assistance with herd management at the UQ Pinjarra Hills Farm. The authors also acknowledge Dr Tim Bruxner from the UQ Institute for Molecular Bioscience for providing services in the Bioanalyser 2100 Instrument, as well as Dr Russell Lyons and Dr Karen Schutt from Neogen Australasia for providing animal genotyping services.

Publisher Copyright:
© The Author(s) 2024.

Keywords

Bovine
Cattle
Gene expression
Host resistance
RNA-Seq

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Cite this

@article{bb904b8520f147f7a6020badcd9146ee,

title = "Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility",

abstract = "The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-na{\"i}ve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR < 0.05), of which 212 were the target of at least 1866 transcription factors (TFs) expressed in skin. Regulatory impact factor (RIF) analysis identified 158 significant TFs (P < 0.05) of which GRHL3, and DTX1 were also DEGs in the experiment. Gene term enrichment showed the significant TFs and DEGs were enriched in processes related to immune response and biological pathways related to host response to infectious diseases. Interferon Type 1-stimulated genes, including MX2, ISG15, MX1, OAS2 were upregulated in low host resistance steers after repeated tick challenge, suggesting dysregulated wound healing and chronic inflammatory skin processes contributing to host susceptibility to ticks. The present study provides an assessment of the bovine skin transcriptome before and after repeated tick challenge and shows that the up-regulation of pro-inflammatory genes is a prominent feature in the skin of tick-susceptible animals. In addition, the identification of transcription factors with high regulatory impact provides insights into the potentially meaningful gene–gene interactions involved in the variation of phenotypes of bovine host resistance to ticks.",

keywords = "Bovine, Cattle, Gene expression, Host resistance, RNA-Seq",

author = "{Mantilla Valdivieso}, {Emily F.} and Ross, {Elizabeth M.} and Ali Raza and Loan Nguyen and Hayes, {Ben J.} and Jonsson, {Nicholas N.} and Peter James and Tabor, {Ala E.}",

note = "Funding Information: This research was funded by the Meat and Livestock Australia Donor Company (MDC) grant P.PSH.0798 supported by the Queensland Department of Agriculture & Fisheries entitled {\textquoteleft}Cattle tick and buffalo fly host genetics, susceptibility to buffalo fly lesions and biomarkers for resistance{\textquoteright}. EFMV was supported by an Australian Government Research Training Program (RTP) Scholarship. Funding Information: The authors thank Tom Conolly, Alison Moore, Muhammad Noman Naseem and Muhammad Karman for assistance with herd management at the UQ Pinjarra Hills Farm. The authors also acknowledge Dr Tim Bruxner from the UQ Institute for Molecular Bioscience for providing services in the Bioanalyser 2100 Instrument, as well as Dr Russell Lyons and Dr Karen Schutt from Neogen Australasia for providing animal genotyping services. Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41598-024-54577-w",

language = "English",

volume = "14",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "nature publishing group",

number = "1",

}

TY - JOUR

T1 - Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility

AU - Mantilla Valdivieso, Emily F.

AU - Ross, Elizabeth M.

AU - Raza, Ali

AU - Nguyen, Loan

AU - Hayes, Ben J.

AU - Jonsson, Nicholas N.

AU - James, Peter

AU - Tabor, Ala E.

N1 - Funding Information: This research was funded by the Meat and Livestock Australia Donor Company (MDC) grant P.PSH.0798 supported by the Queensland Department of Agriculture & Fisheries entitled ‘Cattle tick and buffalo fly host genetics, susceptibility to buffalo fly lesions and biomarkers for resistance’. EFMV was supported by an Australian Government Research Training Program (RTP) Scholarship. Funding Information: The authors thank Tom Conolly, Alison Moore, Muhammad Noman Naseem and Muhammad Karman for assistance with herd management at the UQ Pinjarra Hills Farm. The authors also acknowledge Dr Tim Bruxner from the UQ Institute for Molecular Bioscience for providing services in the Bioanalyser 2100 Instrument, as well as Dr Russell Lyons and Dr Karen Schutt from Neogen Australasia for providing animal genotyping services. Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-naïve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR < 0.05), of which 212 were the target of at least 1866 transcription factors (TFs) expressed in skin. Regulatory impact factor (RIF) analysis identified 158 significant TFs (P < 0.05) of which GRHL3, and DTX1 were also DEGs in the experiment. Gene term enrichment showed the significant TFs and DEGs were enriched in processes related to immune response and biological pathways related to host response to infectious diseases. Interferon Type 1-stimulated genes, including MX2, ISG15, MX1, OAS2 were upregulated in low host resistance steers after repeated tick challenge, suggesting dysregulated wound healing and chronic inflammatory skin processes contributing to host susceptibility to ticks. The present study provides an assessment of the bovine skin transcriptome before and after repeated tick challenge and shows that the up-regulation of pro-inflammatory genes is a prominent feature in the skin of tick-susceptible animals. In addition, the identification of transcription factors with high regulatory impact provides insights into the potentially meaningful gene–gene interactions involved in the variation of phenotypes of bovine host resistance to ticks.

AB - The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-naïve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR < 0.05), of which 212 were the target of at least 1866 transcription factors (TFs) expressed in skin. Regulatory impact factor (RIF) analysis identified 158 significant TFs (P < 0.05) of which GRHL3, and DTX1 were also DEGs in the experiment. Gene term enrichment showed the significant TFs and DEGs were enriched in processes related to immune response and biological pathways related to host response to infectious diseases. Interferon Type 1-stimulated genes, including MX2, ISG15, MX1, OAS2 were upregulated in low host resistance steers after repeated tick challenge, suggesting dysregulated wound healing and chronic inflammatory skin processes contributing to host susceptibility to ticks. The present study provides an assessment of the bovine skin transcriptome before and after repeated tick challenge and shows that the up-regulation of pro-inflammatory genes is a prominent feature in the skin of tick-susceptible animals. In addition, the identification of transcription factors with high regulatory impact provides insights into the potentially meaningful gene–gene interactions involved in the variation of phenotypes of bovine host resistance to ticks.

KW - Bovine

KW - Cattle

KW - Gene expression

KW - Host resistance

KW - RNA-Seq

U2 - 10.1038/s41598-024-54577-w

DO - 10.1038/s41598-024-54577-w

M3 - Journal article

C2 - 38388834

AN - SCOPUS:85185662167

SN - 2045-2322

VL - 14

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 4419

ER -