Cross talk between growth and immunity: coupling of the IGF axis to conserved cytokine pathways in rainbow trout

• Published in: Endocrinology
• Main Authors: Alzaid, Abdullah, Castro, Rosario, Wang, Tiehui, Secombes, Christopher J., Boudinot, Pierre, Macqueen, Daniel J., Martin, Samuel A. M.
• Other Authors: Institute of Biological and Environmental Sciences, University of Aberdeen, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), European Community 442 222719 311993 University of Aberdeen Institut National de la Recherche Agronomique Kuwait University
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2016
• Subjects: FACTOR-BINDING-PROTEINS; ATLANTIC SALMON; TELEOST FISH; ONCORHYNCHUS-MYKISS; TRADE-OFFS; INSULIN; SALMON SALMO-SALAR; TUMOR-NECROSIS-FACTOR; FACTOR-I; PCR DATA; [SDV]Life Sciences [q-bio]; Atlantic salmon; Salmo salar
• Online Access: https://hal.inrae.fr/hal-02635356; https://doi.org/10.1210/en.2015-2024

International audience Although disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterized. We postulated that the 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 after first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, 19 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 down-regulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes, each negative regulators of IGF signaling, were highly induced by AS and VHSv in striking correlation with host defense genes regulated by cytokine pathways. Follow-up experiments demonstrated a highly significant coregulation 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 signaling 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.