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

Autor: Ugolini M; 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 J; 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., Burkert S; 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., Jensen KJ; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs Lyngby, Denmark., Georg P; 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., Ebner F; Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany., Volkers SM; 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., Thada S; 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.; Bhagwan Mahavir Medical Research Centre, Hyderabad, India., Dietert K; Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany., Bauer L; Chronic Immune Reactions, German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany., Schäfer A; Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Island of Riems, Germany., Helbig ET; 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 B; 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.; German Center for Lung Research (DZL), Berlin, Germany., Kurth F; 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., Sur S; 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 N; 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., Gaddam S; Bhagwan Mahavir Medical Research Centre, Hyderabad, India.; Department of Genetics, Osmania University, Hyderabad, India., Conrad ML; 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., Benn CS; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.; Odense Patient Data Explorative Network (OPEN), Odense University Hospital/Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Blohm U; Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Island of Riems, Germany., Gruber AD; Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany., Hutloff A; Chronic Immune Reactions, German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany., Hartmann S; Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany., Boekschoten MV; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands., Müller M; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.; Norwich Medical School, University of East Anglia, Norwich, UK., Jungersen G; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs Lyngby, Denmark., Schumann RR; 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., Suttorp N; 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.; German Center for Lung Research (DZL), Berlin, Germany., Sander LE; 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.; German Center for Lung Research (DZL), Berlin, Germany. leif-erik.sander@charite.de.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2018 Apr; Vol. 19 (4), pp. 386-396. Date of Electronic Publication: 2018 Mar 19.
DOI: 10.1038/s41590-018-0068-4
Abstrakt: 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 (T FH 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 T FH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust T FH 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 T FH cell differentiation and a promising target for T FH cell-skewing vaccine adjuvants.
Databáze: MEDLINE
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