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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-α response to TLR9 triggering


Audigé, A; Schlaepfer, E; von Wyl, V; Miller, R C; Vernazza, P; Nadal, D; Speck, R F (2010). 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. AIDS Research and Human Retroviruses, 26(10):1063-1074.

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-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.

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-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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:15 Jan 2011 14:57
Last Modified:05 Apr 2016 14:35
Publisher:Mary Ann Liebert
ISSN:0889-2229
Additional Information:This is a copy of an article published in the AIDS Research and Human Retroviruses © 2010 copyright Mary Ann Liebert, Inc.; AIDS Research and Human Retroviruses is available online at: http://www.liebertonline.com.
Publisher DOI:https://doi.org/10.1089/aid.2009.0288
PubMed ID:20963937

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