Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α.

Jinjin Zhang,Min Wan,Kangsen Mai,Miao Liu,Hui Zhang,Huiyuan Sun,Yawen Lan

doi:10.3389/fimmu.2020.615536

Abstract

Short-chain fatty acids (SCFAs) are mainly produced by microbiota through the fermentation of carbohydrates in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and have been shown to be important in the maintenance of host health. In this study, head kidney macrophages (HKMs) were isolated and cultured from turbots. We found that the antibacterial activity of HKMs was increased after these cells were incubated with sodium butyrate, sodium propionate or sodium acetate. Interestingly, our results showed that all three SCFAs enhanced the expression of hypoxia inducible factor-1 α (HIF-1α) in HKMs, and further study confirmed that butyrate augmented the oxygen consumption of these cells. Moreover, HIF-1α inhibition diminished the butyrate-promoted intracellular bacterial killing activity of macrophages, and SCFAs also raised the gene expression and activity of lysozymes in HKMs via HIF-1α signaling. In addition, our results suggested that butyrate induced HIF-1α expression and the bactericidal activity of HKMs through histone deacetylase inhibition, while G protein-coupled receptors did not contribute to this effect. Finally, we demonstrated that butyrate induced a similar response in the murine macrophage cell line RAW264.7. In conclusion, our results demonstrated that SCFAs promoted HIF-1α expression via histone deacetylase inhibition, leading to the enhanced production of antibacterial effectors and increased bacterial killing of macrophages.

Highlights

Butyrate, propionate, and acetate, which are collectively called short-chain fatty acids (SCFAs), are products of the microbial fermentation of dietary fiber in the gut
To assess the influence of SCFAs on the bacterial killing ability of turbot head kidney macrophages (HKMs), isolated macrophages were incubated with control buffer, sodium butyrate (NaB), sodium propionate (NaP) or sodium acetate (NaA) at different concentrations (1, 5, 10 mM) for 24 h
The survival rates of E. tarda in HKMs pretreated with NaB (Figure 1A), NaP (Figure 1B) or NaA (Figure 1C) were significantly lower than those in macrophages treated with control buffer

Summary

Introduction

Propionate, and acetate, which are collectively called short-chain fatty acids (SCFAs), are products of the microbial fermentation of dietary fiber in the gut. It is well-known that SCFAs are important energy and signaling molecules, displaying beneficial effects on various physiological processes [1]. The effects of SCFAs and their salts have been highlighted as immune stimulators on the health of aquatic organisms [2, 3]. Tian et al demonstrated that the growth and intestinal immune functions of grass carp (Ctenopharyngodon idella) were improved when fish were fed a butyrate-supplemented diet, and fish receiving butyrate in their diet were protected from Aeromonas hydrophila infection [4]. A recent study from our research group reported that butyrate supplementation in turbot diet significantly alleviated high-soybean meal-induced enteritis [5]

Methods

Results

Conclusion