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The role of Toll-like receptor 10 in modulation of trained immunity.

Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands. Epigenetics Research, Murdoch Children's Research Institute, Parkville, Vic., Australia. Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark. Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, Denmark. Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, The Netherlands. Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

Immunology. 2020;(3):289-297
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Abstract

Toll-like receptor 10 (TLR10) is the only member of the human Toll-like receptor family with an inhibitory function on the induction of innate immune responses and inflammation. However, its role in the modulation of trained immunity (innate immune memory) is unknown. In the present study, we assessed whether TLR10 modulates the induction of trained immunity induced by β-glucan or bacillus Calmette-Guérin (BCG). Interleukin 10 receptor antagonist production was increased upon activation of TLR10 ex vivo after BCG vaccination, and TLR10 protein expression on monocytes was increased after BCG vaccination, whereas anti-TLR10 antibodies did not significantly modulate β-glucan or BCG-induced trained immunity in vitro. A known immunomodulatory TLR10 missense single-nucleotide polymorphism (rs11096957) influenced trained immunity responses by β-glucan or BCG in vitro. However, the in vivo induction of trained immunity by BCG vaccination was not influenced by TLR10 polymorphisms. In conclusion, TLR10 has a limited, non-essential impact on the induction of trained immunity in humans.