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

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 CD56(high)CD16(neg) 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 center dot HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. center dot HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. center dot In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. center dot NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. center dot HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

Automated summary

HLA-B*57 affects the course of HIV infection by modifying inflammatory subsets of NK cells and monocytes, leading to enhanced responsiveness of these innate immune cells to TLR ligands, potentially contributing to increased vulnerability in sepsis.