Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections
| Autor: | Sara Klucking, Ashley P. Barry, Mark B. Feinberg, Franck J. Barrat, Robert L. Coffman, Thomas H. Vanderford, Judith N. Mandl, Rahul Chavan, Natalia Kozyr, Silvija I. Staprans |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Receptors CCR7 viruses animal diseases T cell Molecular Sequence Data Simian Acquired Immunodeficiency Syndrome medicine.disease_cause General Biochemistry Genetics and Molecular Biology Virus Cercocebus atys Immune system medicine Animals Humans Amino Acid Sequence Acquired Immunodeficiency Syndrome Innate immune system biology NF-kappa B Interferon-alpha virus diseases Dendritic Cells General Medicine Simian immunodeficiency virus biology.organism_classification Type I interferon production Macaca mulatta Virology Killer Cells Natural medicine.anatomical_structure Toll-Like Receptor 7 Viral replication Toll-Like Receptor 9 Immunology Sooty mangabey Female Disease Susceptibility Signal Transduction |
| Zdroj: | Nature Medicine. 14:1077-1087 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Pathogenic HIV infections of humans and simian immunodeficiency virus (SIV) infections of rhesus macaques are characterized by generalized immune activation and progressive CD4(+) T cell depletion. In contrast, natural reservoir hosts for SIV, such as sooty mangabeys, do not progress to AIDS and show a lack of aberrant immune activation and preserved CD4(+) T cell populations, despite high levels of SIV replication. Here we show that sooty mangabeys have substantially reduced levels of innate immune system activation in vivo during acute and chronic SIV infection and that sooty mangabey plasmacytoid dendritic cells (pDCs) produce markedly less interferon-alpha in response to SIV and other Toll-like receptor 7 and 9 ligands ex vivo. We propose that chronic stimulation of pDCs by SIV and HIV in non-natural hosts may drive the unrelenting immune system activation and dysfunction underlying AIDS progression. Such a vicious cycle of continuous virus replication and immunopathology is absent in natural sooty mangabey hosts. |
| Databáze: | OpenAIRE |
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