Background: The pathogenesis of cardiovascular disease (CVD) and immune activation in HIV-1 infection is unclear. We have shown that HIV-1 infected subjects have dysfunctional High Density Lipoprotein (dys-HDL) that is associated with macrophage activation, CVD and directly upregulates T cell activation in vitro, a hallmark of chronic HIV-1 infection. Uptake of modified lipoproteins has a major role in the pathogenesis of CVD. CXCL16 is an inflammatory chemokine that shares scavenger receptor function, promoting uptake of modified lipids. Sialoadhesin (Siglec-1) is a lectin-like adhesion molecule expressed on monocytes/macrophages (M/M), which enhances HIV infectivity and also has a role in the uptake of oxidized lipids by M/M. Siglec-1(+) M/M can internalize lipid antigens and present it to invariant natural killer (iNKT) cells, resulting in T cell activation. In view of these data, we investigated whether dys-HDL from HIV-infected subjects may directly upregulate CXCL16 and Siglec-1 mRNA expression in circulating monocytes in vitro.
Methods: Native HDL (known to be dys-HDL based on HDL function assay) was isolated from 5 HIV-1 infected subjects with suppressed viremia on antiretroviral therapy and normal lipid profile (HIV-HDL). HDL from healthy donors was also oxidized (HDLox) in vitro. HDL, HDLox and HIV-HDL were added (6.25 ug/ml) in serum free media to peripheral blood mononuclear cells (PBMCs) isolated from healthy subjects (n=6). mRNA expression of CXCL16 and Siglec-1 were determined using real time PCR. Data were analyzed using paired t-tests.
Results: All HIV infected subjects were male, white with a median age 44 (range 21-56), median CD4+ T cells 514 cells/mm3. Compared to normal HDL, addition of both HIV-HDL and HDLox upregulated mRNA expression of CXCL16 and Siglec-1 (Figures).
Conclusion: Dys-HDL in HIV-infected subjects with suppressed viremia may directly upregulate CXCL16 and Siglec-1 in monocytes. Since Siglec-1 and CXCL16 mediate uptake of lipids and interact with immunity and HIV-1 (Siglec-1), further studies need to elucidate the role of dys-HDL and CXCL16 as novel mechanisms that may contribute to atherosclerosis and immune activation in HIV infection despite successful virologic therapy.
D. Huynh, None
S. Park, None
O. Yang, None