Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: possible implication for TLR4-signalling and chronic immune activation.
Progressive HIV infection is characterized by profound enterocyte damage, microbial translocation and chronic immune activation. We aimed to test whether High Mobility Group Box protein 1(HMGB1), a marker of cell death, alone, or in combination with LPS, might contribute to HIV-associated immune activation and progression. Altogether, 29 untreated HIV-infected individuals, 25 inflammatory bowel disease (IBD) patients and 30 controls were included. HIV-infected patients had lower plasma LPS levels than IBD patients, but higher levels of soluble CD14 and Myeloid Differentiation (MD) 2, which interacts with TLR4 to initiate LPS-signalling. Furthermore, plasma levels of HMGB1 and MD2 were correlated directly within the HIV-infected cohort (r = 0.89, P < 0.001) and the IBD-cohort (r = 0.85, P < 0.001), implying HMGB1 signalling through the MD2/TLR4-pathway. HMGB1 and LPS, although not inter-correlated, were both moderately (r = 0.4) correlated with CD38 density on CD8+ T cells in HIV progressors. The highest levels of CD38 density and MD2 were found in progressors with plasma levels of both LPS and HMGB1 above the fiftieth percentile. Our results could imply that, in some patients, immune activation is triggered by microbial translocation, in some by cell death and in some by HMGB1 in complex with bacterial products through activation of the MD2/TLR4-pathway.
Department of Infectious Diseases, Oslo University Hospital, 0424 Oslo, Norway. troseid@hotmail.com
Marius
M
Trøseid
Andreas
A
Lind
Piotr
P
Nowak
Babilonia
B
Barqasho
Bernt
B
Heger
Idar
I
Lygren
Karin K
KK
Pedersen
Tatsuo
T
Kanda
Hiroyuki
H
Funaoka
Jan K
JK
Damås
Dag
D
Kvale
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D006679:HIV Seropositivity; D024243:HMGB1 Protein / Q000097:blood / Q000276:immunology*; D006801:Humans; D007109:Immunity; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000097:blood; D051218:Lymphocyte Antigen 96 / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D024243:HMGB1 Protein; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4; D051997:ADP-ribosyl Cyclase 1