Surface Translocator Protein 18 kDa (TSPO) Localization on Immune Cells Upon Stimulation with LPS and in ART-treated HIV Subjects

Translocator protein 18 kDa (TSPO) is a well-known outer mitochondrial membrane protein and it is widely used as a biomarker of neuroinflammation and brain injury. Although it is thought that TSPO plays key roles in a multitude of host cell functions, including steroid biosynthesis, apoptosis, generation of reactive oxygen species, and proliferation, some of these functions have recently been questioned. Here, we report the unexpected finding that circulating immune cells differentially express basal levels of TSPO on their cell surface, with a high percentage of monocytes and neutrophils expressing cell surface TSPO. In vitro stimulation of monocytes with LPS significantly increases the frequency of cells with surface TSPO expression in the absence of altered gene expression. Importantly, the LPS increase in TSPO cell surface expression in monocytes appears to be selective for LPS because two other distinct monocyte activators failed to increase the frequency of cells with surface TSPO. Finally, when we quantified immune cell TSPO surface expression in antiretroviral therapy-treated HIV donors, a chronic inflammatory disease, we found significant increases in the frequency of TSPO surface localization, which could be pharmacologically suppressed with ∆ -tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood-based biomarker of inflammation.