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

Zugehörigkeit
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.
Ugolini, Matteo;
Zugehörigkeit
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.
Gerhard, Jenny;
Zugehörigkeit
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.
Burkert, Sanne;
Zugehörigkeit
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
Jensen, Kristoffer Jarlov;
Zugehörigkeit
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.
Georg, Philipp;
Zugehörigkeit
Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
Ebner, Friederike;
Zugehörigkeit
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.
Volkers, Sarah M.;
Zugehörigkeit
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.
Thada, Shruthi;
ORCID
0000-0002-5667-6750
Zugehörigkeit
Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Dietert, Kristina;
Zugehörigkeit
Chronic Immune Reactions, German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany.
Bauer, Laura; Schäfer, Alexander;
Zugehörigkeit
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.
Helbig, Elisa T.;
Zugehörigkeit
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.
Opitz, Bastian;
Zugehörigkeit
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.
Kurth, Florian;
ORCID
0000-0001-7002-628X
Zugehörigkeit
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.
Sur, Saubashya;
Zugehörigkeit
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.
Dittrich, Nickel;
Zugehörigkeit
Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
Gaddam, Sumanlatha;
Zugehörigkeit
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.
Conrad, Melanie L.;
Zugehörigkeit
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
Benn, Christine S.;
GND
12231655X
Zugehörigkeit
.
Blohm, Ulrike;
Zugehörigkeit
Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Gruber, Achim D.;
ORCID
0000-0002-0572-8151
Zugehörigkeit
Chronic Immune Reactions, German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany.
Hutloff, Andreas;
Zugehörigkeit
Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
Hartmann, Susanne;
Zugehörigkeit
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Boekschoten, Mark V.;
ORCID
0000-0002-5930-9905
Zugehörigkeit
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Müller, Michael;
ORCID
0000-0003-3147-6960
Zugehörigkeit
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs Lyngby, Denmark.
Jungersen, Gregers;
Zugehörigkeit
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.
Schumann, Ralf R.;
Zugehörigkeit
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.
Suttorp, Norbert;
ORCID
0000-0002-0476-9947
Zugehörigkeit
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.
Sander, Leif E.

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.

Dateien

Zitieren

Zitierform:
Zitierform konnte nicht geladen werden.

Zugriffsstatistik

Gesamt:
Volltextzugriffe:
Metadatenansicht:
12 Monate:
Volltextzugriffe:
Metadatenansicht:

Rechte

Nutzung und Vervielfältigung:
Alle Rechte vorbehalten