Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout

Abdullah Alzaid, Rosario Castro, Tiehui Wang, Christopher J Secombes, Pierre Boudinot, Daniel J Macqueen, Samuel A M Martin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

While disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterised. We postulated that the insulin-like growth factor (IGF) axis - a central governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding and 3 weeks-post first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, nineteen salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes - each negative regulators of IGF signalling - were highly induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a highly-significant co-upregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signalling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross-talk between conserved pathways regulating teleost growth, development and immunity.

Original languageEnglish
Pages (from-to)1942–1955
Number of pages13
JournalEndocrinology
Volume157
Issue number5
Early online date1 Apr 2016
DOIs
Publication statusPublished - 1 Apr 2016

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Insulin-Like Growth Factor Binding Proteins
Oncorhynchus mykiss
Novirhabdovirus
Somatomedins
Immunity
Aeromonas salmonicida
Cytokines
Growth
Genes
Yersinia ruckeri
Head Kidney
Trout
Infection
Gram-Negative Bacteria
Growth and Development
Growth Hormone
Vertebrates
Immune System
Up-Regulation
Down-Regulation

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Cross Talk Between Growth and Immunity : Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout. / Alzaid, Abdullah; Castro, Rosario; Wang, Tiehui; Secombes, Christopher J; Boudinot, Pierre; Macqueen, Daniel J; Martin, Samuel A M.

In: Endocrinology, Vol. 157, No. 5, 01.04.2016, p. 1942–1955.

Research output: Contribution to journalArticle

Alzaid, Abdullah ; Castro, Rosario ; Wang, Tiehui ; Secombes, Christopher J ; Boudinot, Pierre ; Macqueen, Daniel J ; Martin, Samuel A M. / Cross Talk Between Growth and Immunity : Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout. In: Endocrinology. 2016 ; Vol. 157, No. 5. pp. 1942–1955.
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abstract = "While disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterised. We postulated that the insulin-like growth factor (IGF) axis - a central governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding and 3 weeks-post first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, nineteen salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes - each negative regulators of IGF signalling - were highly induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a highly-significant co-upregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signalling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross-talk between conserved pathways regulating teleost growth, development and immunity.",
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N2 - While disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterised. We postulated that the insulin-like growth factor (IGF) axis - a central governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding and 3 weeks-post first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, nineteen salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes - each negative regulators of IGF signalling - were highly induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a highly-significant co-upregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signalling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross-talk between conserved pathways regulating teleost growth, development and immunity.

AB - While disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterised. We postulated that the insulin-like growth factor (IGF) axis - a central governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding and 3 weeks-post first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, nineteen salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes - each negative regulators of IGF signalling - were highly induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a highly-significant co-upregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signalling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross-talk between conserved pathways regulating teleost growth, development and immunity.

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