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.
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough.
authors.forename: Tristan I
authors.initials: TI
authors.lastname: Evans
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Schafer
authors.affiliation: Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory.
authors.forename: Xing-Pei
authors.initials: XP
authors.lastname: Hao
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Traslavina
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: Program in Barrier Immunity and Repair, Immunopathogenesis Section, LMM, NIAID NIH, Bethesda, Maryland.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: 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.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
mesh_terms: D000818:Animals; D017209:Apoptosis; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006520:Hepatitis, Animal / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007694:Killer Cells, Natural / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000382:microbiology; D008253:Macaca mulatta; D022423:Myeloid Cells / Q000502:physiology*; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D015302:Simian Immunodeficiency Virus
chemical_list: D019743:Chemokines, CXC; D054387:Receptors, CXCR
keywords: HIV; SIV; liver disease; microbial translocation; myeloid dendritic cells; natural killer cells