SIV infection of rhesus macaques differentially impacts mononuclear phagocyte responses to virus-derived TLR agonists

J Med Primatol. 2013 Oct;42(5):247-53. doi: 10.1111/jmp.12064. Epub 2013 Jul 30.

Abstract

Background: During progressive simian immunodeficiency virus (SIV) infection, the ability of innate mononuclear phagocytes to function when responding to the invading pathogen has yet to be determined.

Methods: We generated single-stranded RNA (ssRNA) oligonucleotides from the infecting strain of virus and utilized them to stimulate mononuclear phagocytes from blood and lymph nodes of naïve and SIVmac251-infected rhesus macaques.

Results: Soon after infection and continuing through to chronic disease, plasmacytoid dendritic cells (pDC), monocytes, and macrophages from SIV-infected macaques were less able to produce pro-inflammatory cytokines after exposure to virus-derived toll-like receptor (TLR) agonists. In contrast, myeloid dendritic cells (mDC) became hyper-responsive during acute and stable chronic infection.

Conclusions: Plasmacytoid dendritic cells, monocytes, and macrophages may not instigate continued immune activation by recognizing the single-stranded RNA from SIV as they are left dysfunctional after infection. Conversely, mDC functionality may be beneficial as their hyper-responsiveness is related to slowed disease progression.

Keywords: HIV/AIDS; innate immunity; non-human primate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Animals
  • Chronic Disease
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / virology
  • Macaca mulatta
  • Macrophages / immunology
  • Macrophages / pathology
  • Macrophages / virology
  • Male
  • Monocytes / immunology
  • Monocytes / pathology
  • Monocytes / virology
  • Mononuclear Phagocyte System / immunology
  • Mononuclear Phagocyte System / pathology*
  • Mononuclear Phagocyte System / virology*
  • RNA, Viral / pharmacology
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / metabolism
  • Simian Acquired Immunodeficiency Syndrome / pathology*
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / pathogenicity
  • Toll-Like Receptors / agonists*
  • Toll-Like Receptors / metabolism
  • Toll-Like Receptors / physiology

Substances

  • RNA, Viral
  • Toll-Like Receptors