High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages

• Published in: Scientific reports Vol. 8; no. 1; pp. 6736 - 11
• Main Authors: Inoue, Manabu, Niki, Mamiko, Ozeki, Yuriko, Nagi, Sachiyo, Chadeka, Evans Asena, Yamaguchi, Takehiro, Osada-Oka, Mayuko, Ono, Kenji, Oda, Tetsuya, Mwende, Faith, Kaneko, Yukihiro, Matsumoto, Makoto, Kaneko, Satoshi, Ichinose, Yoshio, Njenga, Sammy M, Hamano, Shinjiro, Matsumoto, Sohkichi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 30.04.2018; Nature Publishing Group UK; Nature Portfolio
• Subjects: High density lipoprotein; Immune response; Infections; Inflammation; Intracellular; Intracellular signalling; Lipids; Liver; Low density lipoprotein; Macrophages; Necrosis; TLR2 protein; Toll-like receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24233-1

Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.