Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology

Stefan Baenziger, Mathias Heikenwalder, Pål Johansen, Erika Schlaepfer, Ursula Hofer, Regina C. Miller, Simone Diemand, Kenya Honda, Thomas M. Kundig, Adriano Aguzzi, Roberto F. Speck

研究成果: Article査読

115 被引用数 (Scopus)


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 oligonucleo-tides - 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 signaling may be a potential strategyto reduce chronic hyper-immune activation and, thereby, disease progression in HIV infection.

出版ステータスPublished - 2009 1月 8

ASJC Scopus subject areas

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学


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