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

Tristan I Evans, Haiying Li, Jamie L Schafer, Nichole R Klatt, Xing-Pei Hao, Ryan P Traslavina, Jacob D Estes, Jason M Brenchley, R Keith Reeves

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)361-9
Number of pages9
JournalThe Journal of infectious diseases
Issue number3
StatePublished - Feb 1 2016
Externally publishedYes

Bibliographical note

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail


  • Animals
  • Apoptosis
  • Chemokines, CXC/genetics
  • Gene Expression Regulation
  • Hepatitis, Animal/etiology
  • Killer Cells, Natural/physiology
  • Liver/metabolism
  • Macaca mulatta
  • Myeloid Cells/physiology
  • Receptors, CXCR/genetics
  • Simian Acquired Immunodeficiency Syndrome/complications
  • Simian Immunodeficiency Virus

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't


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