A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques

J Med Primatol. 2011 Aug;40(4):206-13. doi: 10.1111/j.1600-0684.2011.00484.x. Epub 2011 Jul 1.

Abstract

Background: The mechanism for loss of myeloid dendritic cells (mDCs) from the circulation in HIV-infected individuals and its relationship to disease progression is not understood.

Methods: A longitudinal analysis of the mDC response in blood and lymph nodes during the first 12 weeks of infection was performed in a cohort of SIVmac251-infected rhesus macaques with different disease outcomes.

Results: Monkeys that rapidly progressed to disease or had long-term stable infection had significant losses or increases, respectively, in blood mDCs that were inversely correlated with virus load at set-point. The loss of mDCs from progressor animals was associated with evidence of an increase in CCR7/CCL19-dependent mDC recruitment to lymph nodes and an increase in mDC apoptosis.

Conclusions: mDC recruitment to and death within inflamed lymph nodes may contribute to disease progression in SIV infection, whereas mobilization without increased recruitment to lymph nodes may promote disease control.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / physiopathology
  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Cohort Studies
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Disease Progression
  • Longitudinal Studies
  • Lymph Nodes / immunology
  • Lymph Nodes / physiology
  • Macaca mulatta
  • Myeloid Cells / immunology
  • Predictive Value of Tests
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / physiopathology
  • Simian Immunodeficiency Virus
  • Viral Load