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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6869

Baenziger, S; Heikenwalder, M; Johansen, P; Schlaepfer, E; Hofer, U; Miller, R; Diemand, S; Honda, K; Kundig, T M; Aguzzi, A; Speck, R F (2009). Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood, 113(2):377-388.

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Abstract

Chronic immune activation is a major cause for progressive immunodeficiency in human immunodeficiency virus type-1 (HIV) infection. The underlying trigger, however, remains largely unknown. HIV single-stranded RNA is a potent immune activator by triggering Toll-like receptor (TLR) 7/8. Thus, we hypothesized that sustained TLR7 triggering induces chronic immune activation and thereby contributes to progressive immunodeficiency. We used the synthetic compound R848 or a mixture of uridine-rich HIV single-stranded (ss) RNA oligonucleotides - both are potent TLR7/8 agonists - to explore the effects of sustained TLR7 triggering on the murine lymphoid system. Sustained TLR7 triggering induced an immunopathology reminiscent of progressive lymphoid destruction in HIV disease; we observed lymphopenia, elevated proinflammatory cytokines, splenomegaly, contracted lymphoid subsets, and lymphoid microarchitecture alteration with reduced marginal zone B-lymphocytes. Upon exposure to inactivated vesiculo-stomatitis virus, antibody production was abolished, although splenic lymphocytes were activated and total IgG was elevated. Our data imply that HIV itself may directly contribute to immune activation and dysfunction by stimulating TLR7. Thus, manipulation of TLR7 signalling may be a potential strategy to reduce chronic hyper-immune activation and, thereby, disease progression in HIV infection.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:09 Dec 2008 08:13
Last Modified:27 Nov 2013 23:16
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood, 2009; 112(2):377-388. Copyright by the American Society of Hematology
Publisher DOI:10.1182/blood-2008-04-151712
Official URL:http://bloodjournal.hematologylibrary.org/cgi/reprint/113/2/377
PubMed ID:18824599
Citations:Web of Science®. Times Cited: 63
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Scopus®. Citation Count: 67

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