Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis
Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1265038/full |
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| author | Sajad A. Bhat Sajad A. Bhat Sajad A. Bhat Mahmoud Elnaggar Thomas J. Hall Gillian P. McHugo Cian Reid David E. MacHugh David E. MacHugh Kieran G. Meade Kieran G. Meade Kieran G. Meade |
| author_facet | Sajad A. Bhat Sajad A. Bhat Sajad A. Bhat Mahmoud Elnaggar Thomas J. Hall Gillian P. McHugo Cian Reid David E. MacHugh David E. MacHugh Kieran G. Meade Kieran G. Meade Kieran G. Meade |
| author_sort | Sajad A. Bhat |
| collection | DOAJ |
| description | Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells – a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10–12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ γδ T cell compartment (absolute log2 FC ≥ 1.5 and FDR Padj. ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1+ specific subset in cattle naturally infected with M. bovis. |
| first_indexed | 2024-03-11T16:06:54Z |
| format | Article |
| id | doaj.art-12e73de268d8406192d5e21d3f30bf8f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T16:06:54Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-12e73de268d8406192d5e21d3f30bf8f2023-10-24T23:41:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12650381265038Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovisSajad A. Bhat0Sajad A. Bhat1Sajad A. Bhat2Mahmoud Elnaggar3Thomas J. Hall4Gillian P. McHugo5Cian Reid6David E. MacHugh7David E. MacHugh8Kieran G. Meade9Kieran G. Meade10Kieran G. Meade11UCD School of Agriculture and Food Science, University College Dublin, Dublin, IrelandUCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, IrelandAnimal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Dunsany, IrelandAnimal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Dunsany, IrelandUCD School of Agriculture and Food Science, University College Dublin, Dublin, IrelandUCD School of Agriculture and Food Science, University College Dublin, Dublin, IrelandAnimal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Dunsany, IrelandUCD School of Agriculture and Food Science, University College Dublin, Dublin, IrelandUCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, IrelandUCD School of Agriculture and Food Science, University College Dublin, Dublin, IrelandUCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, IrelandUCD Institute of Food and Health, University College Dublin, Dublin, IrelandBovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells – a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10–12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ γδ T cell compartment (absolute log2 FC ≥ 1.5 and FDR Padj. ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1+ specific subset in cattle naturally infected with M. bovis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1265038/fullWC1+ γδ T cellsnatural Mycobacterium bovisbovineNk receptorsRNA-seq - RNA sequencing |
| spellingShingle | Sajad A. Bhat Sajad A. Bhat Sajad A. Bhat Mahmoud Elnaggar Thomas J. Hall Gillian P. McHugo Cian Reid David E. MacHugh David E. MacHugh Kieran G. Meade Kieran G. Meade Kieran G. Meade Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis Frontiers in Immunology WC1+ γδ T cells natural Mycobacterium bovis bovine Nk receptors RNA-seq - RNA sequencing |
| title | Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis |
| title_full | Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis |
| title_fullStr | Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis |
| title_full_unstemmed | Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis |
| title_short | Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis |
| title_sort | preferential differential gene expression within the wc1 1 γδ t cell compartment in cattle naturally infected with mycobacterium bovis |
| topic | WC1+ γδ T cells natural Mycobacterium bovis bovine Nk receptors RNA-seq - RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1265038/full |
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