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Blood, 8 January 2009, Vol. 113, No. 2, pp. 377-388. Prepublished online as a Blood First Edition Paper on September 29, 2008; DOI 10.1182/blood-2008-04-151712. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-04-151712v1 113/2/377    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Baenziger, S. Articles by Speck, R. F Search for Related Content PubMed PubMed Citation Articles by Baenziger, S. Articles by Speck, R. F Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 15, 2008 Accepted September 8, 2008 Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology Stefan Baenziger, Mathias Heikenwalder, Pal Johansen, Erika Schlaepfer, Ursula Hofer, Regina C Miller, Simone Diemand, Kenya Honda, Thomas M Kundig, Adriano Aguzzi, and Roberto F Speck* Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland Department of Dermatology, University Hospital Zurich, Zurich, Switzerland Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan * Corresponding author; email: roberto.speck{at}usz.ch. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: TLR-mediated immune activation in HIV J. Judy Chang and Marcus Altfeld Blood 2009 113: 269-270. [Full Text] [PDF]

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