TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients

J Mol Med (Berl). 2021 Jan;99(1):147-158. doi: 10.1007/s00109-020-01996-7. Epub 2020 Dec 5.


HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. KEY MESSAGES: • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

Keywords: Bacterial infections; HIV; HLA-B*57; Inflammatory immune response; Toll-like receptor stimulation; cART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / immunology
  • Female
  • HIV Infections / immunology*
  • HLA-B Antigens / immunology*
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lipopeptides / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Oligodeoxyribonucleotides / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptors / agonists*
  • Young Adult


  • CpG ODN 2216
  • Cytokines
  • HLA-B Antigens
  • HLA-B57 antigen
  • Lipopeptides
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Pam(3)CSK(4) peptide
  • Toll-Like Receptor 9
  • Toll-Like Receptors