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Title: Regulation of lentivirus neurovirulence by lipopolysaccharide conditioning: Suppression of CXCL10 in the brain by IL-10
Authors: Ferdinand Maingat
Serena Viappiani
Yu Zhu
Pornpun Vivithanaporn
Kristofor K. Ellestad
Janet Holden
Claudia Silva
Christopher Power
University of Alberta
University of Calgary
St. Paul's Hospital
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 1-Feb-2010
Citation: Journal of Immunology. Vol.184, No.3 (2010), 1566-1574
Abstract: Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause neurovirulence, which is largely mediated by innate immunity. To investigate the interactions between neurovirulence and repeated conditioning by innate immune activation, models of lentivirus infection were exposed to LPS. Gene expression in HIV-infected (HIV+) and control (HIV-) patient brains was compared by real time RT-PCR and immunocytochemistry. Supernatants from mock and HIV-infected monocyte-derived macrophages exposed to LPS were applied to human neurons. FIV-infected (FIV+) and control (FIV-) animals were exposed repeatedly to LPS postinfection together with concurrent neurobehavioral testing, viral load, and host gene analyses. Brains from HIV+ individuals exhibited induction of CD3ε, CXCL10, and granzyme A expression (p < 0.05). Supernatants from HIV+ monocyte-derived macrophages induced CXCL10 expression in neurons, which was diminished by IL-10 treatment (p < 0.05). LPS-exposed FIV+ animals demonstrated lower plasma and brain viral loads (p < 0.05). Neuronal CXCL10 expression was increased in FIV+ animals but was suppressed by LPS exposure, together with reduced brain CD3ε and granzyme A expression (p < 0.05). In conjunction with preserved NeuN-positive neuronal counts in parietal cortex (p < 0.05), FIV+ animals exposed to LPS also showed less severe neurobehavioral deficits (p < 0.05). Repeated LPS exposures suppressed CXCL10 in the brain and ensuing T cell infiltration with a concomitant reduction in neurovirulence. Thus, innate immune chronic conditioning exerted beneficial effects on neurovirulence through suppression of a specific chemotactic factor, CXCL10, mediated by IL-10, leading to reduced leukocyte infiltration and release of neurotoxic factors. Copyright © 2010 by The American Association of Immunologists, Inc.
ISSN: 15506606
Appears in Collections:Scopus 2006-2010

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