Sialoadhesin (CD169) expression in CD14+ cells is upregulated early after HIV-1 infection and increases during
Antoinette C van der Kuyl1, Remco van den Burg, Fokla Zorgdrager
1Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands. a.c.vanderkuyl@amc.uva.nl
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.
Insights
Sialoadhesin (CD169) levels increase early in HIV-1 infection on CD14+ cells. This marker is maintained during disease progression and may indicate infection and immune dysregulation in AIDS.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Sialoadhesin (CD169) is an activation marker on macrophages, notably in chronic inflammation, tumors, and Kaposi's sarcoma lesions.
- Elevated CD169 expression is observed on monocytes in HIV-1 infected individuals with high viral loads, even with treatment.
Purpose of the Study:
- To investigate sialoadhesin expression in untreated HIV-1 and HHV-8 infected patients.
- To correlate sialoadhesin levels with HIV-1 infection status and disease progression.
Main Methods:
- Real-time PCR and Flow Cytometry (FACS) analysis were employed.
- Patient groups included HIV-1 seroconverters, chronic HIV-1, and AIDS stages, with HHV-8 infected and uninfected controls.
Main Results:
- Sialoadhesin mRNA significantly increased post-HIV-1 infection, with further elevation in AIDS patients, but not after HHV-8 infection.
- Sialoadhesin levels rise early, around HIV-1 seroconversion.
- FACS showed high sialoadhesin protein on ~90% of CD14+ and CD14+CD16+ cells in HIV-1(+) patients, a 10-fold increase per cell.
Conclusions:
- Sialoadhesin is induced on CD14+ cells early in HIV-1 infection in vivo.
- The observed cell phenotype persists throughout disease progression.
- Sialoadhesin may serve as an early marker for HIV-1 infection and contribute to immune dysregulation in AIDS.
