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

Abstract

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.

Authors: Dold L, Zimmer L, Schwarze-Zander C, Boesecke C, Mohr R, Wasmuth JC, Ommer K, Gathof B, Krämer B, Nattermann J, Strassburg CP, Rockstroh JK, Spengler U, Langhans B,
Journal: J Mol Med (Berl); 2021 Jan;99(1):147-158 . doi:10.1007/s00109-020-01996-7
Year: 2021
PubMed: PMID: 33278000 (Go to PubMed)