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


RESULTS
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
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.
van der Kuyl
Antoinette C
AC
Laboratory 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
van den Burg
Remco
R
Zorgdrager
Fokla
F
Groot
Fedde
F
Berkhout
Ben
B
Cornelissen
Marion
M
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1; D019288:Herpesvirus 8, Human; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D015854:Up-Regulation; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1