1235. Dysfunctional HDL in HIV-infected adults with suppressed viremia on antiretroviral therapy may directly increase mRNA expression of CXCL16 and sialoadhesin in monocytes
Session: Poster Abstract Session: Viral Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall

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.

Theodoros Kelesidis, MD, PhD1, Stefanie Homann, PhD2, Diana Huynh, BS3, Sangeun Park, BS2 and Otto Yang, MD4, (1)David Geffen School of Medicine at UCLA, Los Angeles, CA, (2)David Geffen School of Medicine at UCLA, Los Angeles, CA, (3)David Geffen School of Medicine at UCLA, los angeles, CA, (4)David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA

Disclosures:

T. Kelesidis, None

S. Homann, None

D. Huynh, None

S. Park, None

O. Yang, None

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