Abstract:
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 proinflammatory 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.