Polyunsaturated Fatty Acids Influence LPS-Induced Inflammation of Fish Macrophages Through Differential Modulation of Pathogen Recognition and p38 MAPK/NF-κB Signaling.

Qingfei Li,Kun Cui,Qinghui Ai,Kangsen Mai,Dan Xu,Mengjiao Wu

doi:10.3389/fimmu.2020.559332

Abstract

Polyunsaturated fatty acids (PUFAs) not only serve as essential nutrients but also function as modulators of the immune response in marine fish. However, their immunomodulatory mechanism is poorly understood given that the underlying regulation of the innate immune response in fish has not been fully elucidated. Hence, study of the innate immunity of fish could help elucidate the mechanism by which PUFAs affect the fish immune response. Here, we used combined transcriptome analysis and in vitro experimentation to study the mechanism of LPS-induced inflammation. Transcriptome profiling indicated that LPS elicited strong pro-inflammatory responses featuring high expression levels of pathogen recognition receptors (PRRs) and cytokines along with the activation of NF-κB and MAPK signaling pathways. The transcription factor p65 alone could increase the transcription of IL1β by binding to the promoter of IL1β, and this promoting effect disappeared after mutation or deletion of its binding sites. We then examined the effects of PUFAs on the levels of gene expression and the abundance of proteins of critical kinases associated with LPS-induced inflammation. We found that LA exerts pro-inflammatory response while ALA, EPA, and DHA induced anti-inflammatory effects by modulating the expression of PRRs, phosphorylation of IKK and p38, and the nuclear translocation of p65. Overall, this study advances our understanding of the regulatory mechanisms by which PUFAs regulate LPS-induced inflammation in a non-model fish species.

Highlights

The aquaculture industry is facing global shortfalls in the supply of fish oil
Because of the potency and economic benefits of polyunsaturated fatty acids (PUFAs), study of the immunomodulatory effects of PUFAs has become a major focus of research, and a central goal of this research is to improve the health of fish and their resistance to pathogens. w-6 PUFAs are widely known to exert pro-inflammatory effects, while w-3 PUFAs are known to have anti-inflammatory properties through a wide range of mechanisms, including (i) differential modulation of the expression of pathogen recognition receptors (PRRs) [2]; (ii) regulation of signaling pathway activities; and (iii) production of lipid mediators that modify the functions of immune cells
Innate immunity is the first line of defense against microbial pathogens, and the study of innate immunity to bacteria has focused heavily on the mechanisms by which immune cells deal with LPS, the conserved pathogenassociated molecular patterns (PAMPs) of Gramnegative bacteria [24]

Summary

Introduction

The aquaculture industry is facing global shortfalls in the supply of fish oil. With its relatively considerable output, lower price, and relatively high content of polyunsaturated fatty acids (PUFAs), vegetable oil is a promising alternative to fish oil (rich in w-3 PUFAs). Replacing fish oil with vegetable oil in fish diets can result in substantial variation in the dietary composition of fatty acids, altering the immunological responses of fish to infections [1]. Because of the potency and economic benefits of PUFAs, study of the immunomodulatory effects of PUFAs has become a major focus of research, and a central goal of this research is to improve the health of fish and their resistance to pathogens. The mechanism by which individual fatty acids affect fish inflammation remains unclear

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