@article{93cb5e6e1e55444686da24cfa30d03be,
title = "SIV-induced translocation of bacterial products in the liver mobilizes myeloid dendritic and natural killer cells associated with liver damage",
abstract = "Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)-infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage.",
keywords = "HIV, SIV, liver disease, microbial translocation, myeloid dendritic cells, natural killer cells",
author = "Evans, {Tristan I.} and Haiying Li and Schafer, {Jamie L.} and Klatt, {Nichole R.} and Hao, {Xing Pei} and Traslavina, {Ryan P.} and Estes, {Jacob D.} and Brenchley, {Jason M.} and Reeves, {R. Keith}",
note = "Funding Information: The authors thank Michelle Connole, Fay E. Wong, and Yi Yu for expert technical assistance; Angela Carville and Elaine Roberts for dedicated animal care; and Jeff Lifson and Michael Piatak, Jr, of the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc, Frederick National Laboratory, for plasma SIV RNA determinations. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government. This work was supported by Center for HIV/AIDS Vaccine Immunology (CHAVI)/HIV Vaccine Trials Network (HVTN) Early Career Investigator (National Institutes of Health [NIH] grant U19 AI067854), American Foundation for AIDS Research (amFAR) (108547- 53-RGRL), Center for Aids Research (CFAR) Developmental (P30 AI060354), and NIH (R21 AI118468) grants to R. K. R. Funding for this study was provided in part by the Division of Intramural Research/ National Institute of Allergy and Infectious Diseases/NIH and with federal funds from the National Cancer Institute, NIH, under Contract No. HHSN261200800001E. Publisher Copyright: {\textcopyright} The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.",
year = "2016",
month = feb,
day = "1",
doi = "10.1093/infdis/jiv404",
language = "English (US)",
volume = "213",
pages = "361--369",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",
}