STAT3/SOCS3 axis contributes to the outcome of salmonid whirling disease.

Mona Saleh,Mansour El-Matbouli,Adina Friedl,Hatem Soliman,Christopher J Secombes,Mitaly Srivastava,Pierre Boudinot

doi:10.1371/journal.pone.0234479

Mona Saleh, Mansour El-Matbouli + Show 5 more

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https://doi.org/10.1371/journal.pone.0234479

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Abstract

There are differences in disease susceptibility to whirling disease (WD) among strains of rainbow trout. The North American strain Trout Lodge (TL) is highly susceptible, whereas the German Hofer (HO) strain is more resistant. The suppressor of cytokine signaling (SOCS) proteins are key in inhibiting cytokine signaling. Their role in modulating the immune response against whirling disease is not completely clear. This study aimed at investigating the transcriptional response of SOCS1 and SOCS3 genes to Myxobolus cerebralis along with that of several upstream regulators and immune response genes. M. cerebralis induced the expression of SOCS1, the IL-6-dependent SOCS3, the anti-inflammatory cytokine IL-10 and the Treg associated transcription factor FOXP3 in TL fish at multiple time points, which likely caused a restricted STAT1 and STAT3 activity affecting the Th17/Treg17 balance. The expression of SOCS1 and the IL-6-dependent SOCS3 was induced constraining the activation of STAT1 and STAT3 in TL fish, thereby causing Th17/Treg17 imbalance and leaving the fish unable to establish a protective immune response against M. cerebralis or control inflammatory reactions increasing susceptibility to WD. Conversely, in HO fish, the expression of SOCS1 and SOCS3 was restrained, whereas the expression of STAT1 and IL-23-mediated STAT3 was induced potentially enabling more controlled immune responses, accelerating parasite clearance and elevating resistance. The induced expression of STAT1 and IL-23-mediated STAT3 likely maintained a successful Th17/Treg17 balance and enabled fish to promote effective immune responses favouring resistance against WD. The results provide insights into the role of SOCS1 and SOCS3 in regulating the activation and magnitude of host immunity in rainbow trout, which may help us understand the mechanisms that underlie the variation in resistance to WD.

Highlights

Myxobolus cerebralis infects several salmonid species causing whirling disease (WD)
In Trout Lodge (TL) fish the expression of SOCS1 and the IL-6-dependent SOCS3 increased, whereas the expression of STAT1 and STAT3 decreased at the majority of time points post-infection, likely impacting the ability to execute a protective immune response against M. cerebralis
SOCS1 and SOCS3 potentially constrain the expression of STAT1 and STAT3 in TL causing Th17/Treg17 imbalance, leaving fish unable to reduce parasite burden or control inflammatory reactions

Summary

Introduction

Myxobolus cerebralis infects several salmonid species causing whirling disease (WD). Salmonids show variable susceptibility to WD and rainbow trout is the most susceptible species. Several transcriptional studies have provided important insights into the mechanisms utilized by myxozoan parasites to evade the fish immune system [14] Some of these studies aimed to reveal the mechanisms involved in disease resistance [6,7,8,9,10]. Quantitative genetic and genome wide mapping studies have emphasized that a single quantitative trait locus (QTL), Omy, may explain the phenotypic variance of WD resistance in rainbow trout [16,17] This does not rule out that other genes may exhibit critical functions in the fish response to M. cerebralis infection that are not present in the specific Omy region [10]

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