B cells from HIV-infected patients with primary central nervous system lymphoma display an activated phenotype and have a blunted TNF-α response to TLR9 triggering.
Each cell in HIV-associated primary central nervous system lymphoma (PCNSL) harbors latent EBV. Notably, the triggering of TLR9, a key event in HIV pathogenesis, also promotes EBV latency and transformation. We hypothesized that because only a minority of HIV-infected patients develops PCNSL, their B cells exhibit aberrant signaling responses to TLR9 triggering. We found higher levels of IL-6, CD80, and CD86 expression at baseline in B cells of those patients than in B cells of matched controls, whereas TNF-a expression was lower. Notably, on TLR9 triggering with CpG 2006, CD80 and TNF-α were up-regulated to a lesser extent in B cells of the former than in those of matched controls. The reduced up-regulation of CD80 might be explained by its higher baseline expression resulting in a more blunted response rather than a specific deficit of the signaling response to TLR9 triggering. However, this cannot explain the blunted TNF-α response, which warrants further investigation. Finally, since increased IL-6 expression is linked to EBV-associated Hodgkin’s lymphoma, the enhanced baseline expression of IL-6 might be important in the pathogenesis of PCNSL in HIV-infected patients.
Division of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
Annette
A
Audigé
Erika
E
Schlaepfer
Viktor
V
von Wyl
Regina C
RC
Miller
Pietro
P
Vernazza
David
D
Nadal
Roberto F
RF
Speck
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C513533:CpG ODN 2006; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha