Frontline science: HIV infection of Kupffer cells results in an amplified proinflammatory response to LPS

Arevik Mosoian, Lumin Zhang, Feng Hong, Francesc Cunyat, Adeeb Rahman, Riti Bhalla, Ankur Panchal, Yedidya Saiman, M. Isabel Fiel, Sander Florman, Sasan Roayaie, Myron Schwartz, Andrea Branch, Mario Stevenson, Meena B. Bansal

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

End-stage liver disease is a common cause of non-AIDS-related mortality in HIV+ patients, despite effective antiretroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner. We showed that HIV-1 productively infected KCs, enhanced cell-surface TLR4 and CD14 expression, and increased IL-6 and TNF-α expression, which was blocked by a small molecule TLR4 inhibitor. Our study demonstrated that HIV infection sensitizes KCs to the proinflammatory effects of LPS in a TLR4-dependent manner. These findings suggest that HIV-1-infected KCs and their dysregulated innate immune response to LPS may play a role in hepatic inflammation and fibrosis and represent a novel target for therapy.

Original languageEnglish (US)
Pages (from-to)1083-1090
Number of pages8
JournalJournal of Leukocyte Biology
Volume101
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • HIV-induced hepatic inflammation
  • Liver fibrosis
  • Microbial translocation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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