Sialoadhesin (CD169) expression in CD14+ cells is upregulated early after HIV-1 infection and increases during disease progression

Abstract

Background: Sialoadhesin (CD169, siglec-1 or Sn) is an activation marker seen on macrophages in chronic inflammatory diseases and in tumours, and on subsets of tissue macrophages. CD169 is highly expressed by macrophages present in AIDS-related Kaposi's sarcoma lesions. It is also increased on blood monocytes of HIV-1 infected patients with a high viral load despite antiretroviral treatment.

Methodology/principal findings: We investigated expression of sialoadhesin in untreated HIV-1 and HHV-8 infected patients, by real-time PCR and FACS analysis to establish its expression in relation to infection and disease progression. Patients analysed were either HIV-1 seroconverters (n = 7), in the chronic phase of HIV-1 infection (n = 21), or in the AIDS stage (n = 58). Controls were HHV-8 infected, but otherwise healthy individuals (n = 20), and uninfected men having sex with men (n = 24). Sialoadhesin mRNA was significantly elevated after HIV-1, but not HHV-8 infection, and a further increase was seen in AIDS patients. Samples obtained around HIV-1 seroconversion indicated that sialoadhesin levels go up early in infection. FACS analysis of PBMCs showed that sialoadhesin protein was expressed at high levels by approximately 90% of CD14(+) and CD14(+)CD16(+)cells of HIV-1(+) patients with a concomitant 10-fold increase in sialoadhesin protein/cell compared with uninfected controls.

Conclusions/significance: We have shown that sialoadhesin is induced to high levels on CD14(+) cells early after HIV-1 infection in vivo. The phenotype of the cells is maintained during disease progression, suggesting that it could serve as a marker for infection and probably contributes to the severe dysregulation of the immune system seen in AIDS.

Figure 1. Real-time PCR analysis of sialoadhesin mRNA levels in PBMCs of HIV-1 infected patients and controls.

A. Real-time PCR analysis of sialoadhesin mRNA levels in PBMCs derived from five sets of patients with or without HIV-1 infection at different stages of disease. Patients with AIDS but not AIDS-KS, and patients with AIDS-KS were analysed separately. Levels were significantly different (p≤0.0005) between uninfected controls/HHV-8 infected patients, and HIV-1 infected patients, respectively. Levels were also significantly different (p≤0.0005) between HIV-1 infected patients and AIDS patients. Significant differences are indicated with an asterisk. No significant differences were found between patient groups not infected with HIV-1 (p = 0.1), or between AIDS and AIDS-KS patients (p = 0.14). B. Real-time PCR analysis of HIV-1 mRNA levels in PBMCs derived from either HIV-1 infected asymptomatic patients or patients with AIDS (including AIDS-KS). The elevated HIV-1 load in AIDS patients compared to asymptomatic HIV-1⁺ patients is highly significant (p≤0.0001). C. Real-time PCR analysis of sialoadhesin mRNA levels in PBMCs obtained from eight patients before and after HIV-1 seroconversion. Sialoadhesin mRNA was analysed in the first HIV-1 seropositive sample of each patient, which is within three months from the real seroconversion event in the Amsterdam Cohort Studies on HIV/AIDS, as samples are taken on a three-monthly basis.

Figure 2. Expression of CD14, CD16, and sialoadhesin on monocytes from an HIV-1 infected and uninfected patient.

A. Sialoadhesin (CD169) expression on CD14⁺ cells from a healthy human control (left) and an HIV-1 infected patient (right). The mean fluorescent intensity of CD169 from the CD14⁺ cells increases from 26 in the control cells (left) to 286 in the cells from the HIV-1 infected patient (right). B. CD14⁺CD16⁺ cells were gated and their expression of sialoadhesin is shown in the histograms. The mean fluorescent intensity of CD169 from the CD14⁺CD16⁺ cells increases from 17 in the control cells (left) to 158 in the cells from the HIV-1 infected patient (right). The data are representative of three experiments.