Studies on toll-like receptor stimuli responsiveness in HIV-1 and HIV-2 infections.
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-alpha 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.
Department of Virology, The Swedish Institute for Infectious Disease Control, Nobelsväg 18, 171 82 Solna, Sweden.
Salma
S
Nowroozalizadeh
Fredrik
F
Månsson
Zacarias
Z
da Silva
Johanna
J
Repits
Braima
B
Dabo
Carla
C
Pereira
Antonio
A
Biague
Jan
J
Albert
Jens
J
Nielsen
Peter
P
Aaby
Eva Maria
EM
Fenyö
Hans
H
Norrgren
Birgitta
B
Holmgren
Marianne
M
Jansson
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006169:Guinea-Bissau; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000276:immunology*; D012737:Sex Factors; D051193:Toll-Like Receptors / Q000276:immunology*; D019562:Viral Load
D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D020033:Protein Isoforms; D051193:Toll-Like Receptors