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 Klatt, Xing Pei Hao, Ryan P. Traslavina, Jacob D. Estes, Jason M. Brenchley, R. Keith Reeves

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

Bacterial Translocation
Simian Immunodeficiency Virus
Natural Killer Cells
Liver
Lentivirus Infections
Chemotactic Factors
Macaca
Myeloid Cells
Dendritic Cells
Hepatitis
Intestines
Fibrosis
Epithelium
Antigens

Keywords

  • HIV
  • liver disease
  • microbial translocation
  • myeloid dendritic cells
  • natural killer cells
  • SIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

SIV-induced translocation of bacterial products in the liver mobilizes myeloid dendritic and natural killer cells associated with liver damage. / Evans, Tristan I.; Li, Haiying; Schafer, Jamie L.; Klatt, Nichole; Hao, Xing Pei; Traslavina, Ryan P.; Estes, Jacob D.; Brenchley, Jason M.; Reeves, R. Keith.

In: Journal of Infectious Diseases, Vol. 213, No. 3, 01.02.2016, p. 361-369.

Research output: Contribution to journalArticle

Evans, Tristan I. ; Li, Haiying ; Schafer, Jamie L. ; Klatt, Nichole ; Hao, Xing Pei ; Traslavina, Ryan P. ; Estes, Jacob D. ; Brenchley, Jason M. ; Reeves, R. Keith. / SIV-induced translocation of bacterial products in the liver mobilizes myeloid dendritic and natural killer cells associated with liver damage. In: Journal of Infectious Diseases. 2016 ; Vol. 213, No. 3. pp. 361-369.
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