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Nat Immunol. 2018 Apr;19(4):386-396. doi: 10.1038/s41590-018-0068-4. Epub 2018 Mar 19.

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses.

Author information

1
Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
2
Institute of Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
3
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
4
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs Lyngby, Denmark.
5
Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
6
Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
7
Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
8
Chronic Immune Reactions, German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany.
9
Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Island of Riems, Germany.
10
German Center for Lung Research (DZL), Berlin, Germany.
11
Department of Genetics, Osmania University, Hyderabad, India.
12
Department of Internal Medicine and Dermatology, Division of Psychosomatic Medicine, Charite-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
13
Odense Patient Data Explorative Network (OPEN), Odense University Hospital/Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
14
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
15
Norwich Medical School, University of East Anglia, Norwich, UK.
16
Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. leif-erik.sander@charite.de.
17
German Center for Lung Research (DZL), Berlin, Germany. leif-erik.sander@charite.de.

Abstract

Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFH cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of TFH cell differentiation and a promising target for TFH cell-skewing vaccine adjuvants.

PMID:
29556002
DOI:
10.1038/s41590-018-0068-4

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