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    Recognition of microbial viability via TLR8 drives TFHcell differentiation and vaccine responses (2018)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Ugolini, Matteo
    Gerhard, Jenny
    Burkert, Sanne
    Jensen, Kristoffer Jarlov
    Georg, Philipp
    Ebner, Friederike (WE 6)
    Volkers, Sarah M
    Thada, Shruthi
    Dietert, Kristina (WE 12)
    Bauer, Laura
    Schäfer, Alexander
    Helbig, Elisa T
    Opitz, Bastian
    Kurth, Florian
    Sur, Saubashya
    Dittrich, Nickel
    Gaddam, Sumanlatha
    Conrad, Melanie L
    Benn, Christine S
    Blohm, Ulrike
    Gruber, Achim D (WE 12)
    Hutloff, Andreas
    Hartmann, Susanne (WE 6)
    Boekschoten, Mark V
    Müller, Michael
    Jungersen, Gregers
    Schumann, Ralf R
    Suttorp, Norbert
    Sander, Leif E
    Quelle
    Nature immunology; 19(4) — S. 386–396
    ISSN: 1529-2916
    Sprache
    Englisch
    Verweise
    DOI: 10.1038/s41590-018-0068-4
    Pubmed: 29556002
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    Abstract / Zusammenfassung

    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 (TFHcell) 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 TFHcell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFHcell 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 TFHcell differentiation and a promising target for TFHcell-skewing vaccine adjuvants.