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J Infect Dis. 2016 Feb 1;213(3):361-9. doi: 10.1093/infdis/jiv404. Epub 2015 Aug 3.

SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage.

Author information

1
Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
3
Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle.
4
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory.
5
Program in Barrier Immunity and Repair, Immunopathogenesis Section, LMM, NIAID NIH, Bethesda, Maryland.
6
Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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

PMID:
26238685
PMCID:
PMC4704667
DOI:
10.1093/infdis/jiv404
[Indexed for MEDLINE]
Free PMC Article

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