Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection

Jinrui Xu,Cuiping Lv,Yujiong Wang,Xiaoming Liu,Yanbing Zhou,Yi Yang

doi:10.1186/s12865-020-00356-x

Abstract

BackgroundUnderstanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis (M. tuberculosis, Mtb) infection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis bacillus Calmette–Guérin (BCG).ResultsThe results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to a BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection.ConclusionThis study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections.

Highlights

Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide
Alterations of ABC-transporters and ACAT1 in BCGinfected macrophages For further understanding the immune response macrophage induced by Mycobacterium tuberculosis infection at molecular levels, we analyzed RNA-Seq data in bovine alveolar macrophage (AM) at 12 h post a bacillus Calmette–Guérin (BCG) infection
The ATP binding cassette subfamily A member 5 (ABCA5) was reported to correlate with cholesterol efflux in macrophage, while little is known about functions of ATP binding cassette subfamily A member 6 (ABCA6) and ATP binding cassette subfamily A member 10 (ABCA10) [27], suggesting the BCG-altered ABC transporters may have an important implication in the regulation of intracellular cholesterol in macrophages

Summary

Introduction

Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis (M. tuberculosis, Mtb) infection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis bacillus Calmette–Guérin (BCG). Cholesterol metabolism is central to Mtb’s unusual ability to survive in macrophages and provide insights into potential targets for novel therapeutics [12, 13]. In this regard, the metabolic imbalance caused by an infection of Mtb leads the formation of lipid droplets in macrophages, and the accumulation of lipids forms in foam cells, in order to provide a sufficient energy source for the Mycobacteria survival in host cells [14]. We sought to determine whether BCG-induced autophagy was able to be mediated by cholesterol metabolism

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Conclusion