Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-10

AUTHORS

Judith N Mandl, Ashley P Barry, Thomas H Vanderford, Natalia Kozyr, Rahul Chavan, Sara Klucking, Franck J Barrat, Robert L Coffman, Silvija I Staprans, Mark B Feinberg

ABSTRACT

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. More... »

PAGES

1077-1087

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.1871

DOI

http://dx.doi.org/10.1038/nm.1871

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019300068

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18806803


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