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B cells from HIV-infected patients with primary central nervous system lymphoma display an activated phenotype and have a blunted TNF- response to TLR9 triggering
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
1196633
Author(s)
Audigé, Annette; Schlaepfer, Erika; von Wyl, Viktor; Miller, Regina C; Vernazza, Pietro; Nadal, David; Speck, Roberto F; SHCS
B cells from HIV-infected patients with primary central nervous system lymphoma display an activated phenotype and have a blunted TNF- response to TLR9 triggering
Journal
AIDS Research and Human Retroviruses
Volume
26
Number
10
Pages / Article-Number
1063-74
Abstract
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- 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- 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.