Posted by: Indonesian Children | August 15, 2009

Studies on toll-like receptor stimuli responsiveness in HIV-1 and HIV-2 infections

Salma Nowroozalizadeha, b, Fredrik Månssonc, Zacarias da Silvad, e, Johanna Repitsf, Braima Daboe, Carla Pereirae, Antonio Biaguee, Jan Alberta, b, Jens Nielsend, Peter Aabyd, Eva Maria Fenyöf, Hans Norrgrenc, Birgitta Holmgrenf and Marianne Janssona, b, f, Corresponding Author Contact Information, E-mail The Corresponding Author

aDept. of Virology, The Swedish Institute for Infectious Disease Control, Nobelsväg 18, 171 82 Solna, Sweden

bDept. of Microbiology Tumor & Cell biology, Karolinska Institute, Stockholm, Sweden

cInfectious Diseases Research Unit, Dept. of Clinical Sciences, Lund University, Malmö, Sweden

dBandim Health Project, INDEPTH Network, Danish Epidemiology Science Centre, Bissau, Guinea-Bissau

eThe National Laboratory for Public Health, Bissau, Guinea-Bissau

fDept. of Laboratory Medicine, Lund University, Lund, Sweden

Received 24 November 2008; 

accepted 2 March 2009. 

Available online 17 April 2009.



Background: HIV-1 and HIV-2 are two related viruses with distinct clinical outcomes, where HIV-1 is more pathogenic and transmissible than HIV-2. The pathogenesis of both infections is influenced by the dysregulation and deterioration of the adaptive immune system. However, their effects on the responsiveness of innate immunity are less well known. Here, we report on toll-like receptor (TLR) stimuli responsiveness in HIV-1 or HIV-2 infections. Methods: Whole blood from 235 individuals living in Guinea-Bissau who were uninfected, infected with HIV-1, infected with HIV-2, and/or infected with HTLV-I, was stimulated with TLR7/8 and TLR9 agonists, R-848 and unmethylated CpG DNA. After TLR7/8 and TLR9 stimuli, the expression levels of IL-12 and IFN-α were related to gender, age, infection status, CD4+ T cell counts, and plasma viral load. Results: Defective TLR9 responsiveness was observed in the advanced disease stage, along with CD4+ T cell loss in both HIV-1 and HIV-2 infections. Moreover, TLR7/8 responsiveness was reduced in HIV-1 infected individuals compared with uninfected controls. Conclusions: Innate immunity responsiveness can be monitored by whole blood stimulation. Both advanced HIV-1 and HIV-2 infections may cause innate immunity dysregulation.

Keywords: HIV-1; HIV-2; Toll-like receptors; IFN-alpha; IL-12

Article Outline

1. Introduction
2. Materials and methods

2.1. Study population
2.2. Serological determination of HIV-1, HIV-2 and HTLV-I infection status
2.3. Analysis of CD4+ T cell counts and plasma viral load
2.4. Whole blood stimulation assay
2.5. Statistical analysis
3. Results

3.1. Immunological and virological characteristics of the study cohort
3.2. TLR9 responsiveness assessed as IFN-α expression in whole blood after CpG stimuli
3.3. Defective TLR9 responsiveness is associated with reduced CD4+ T cell counts in both HIV-1 and HIV-2 infections
3.4. Reduced IL-12 expression in whole blood of HIV-1 infected after TLR7/8 stimulation
3.5. TLR7/8 or TLR9 responsiveness is not significantly associated with HTLV-I status
3.6. Gender influences TLR responsiveness
4. Discussion


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