Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses
| Autor: | Andrea Cerutti, Matthew Geswell, Irina Leonardi, Leif E. Sander, Iliyan D. Iliev, J. Magarian Blander, Gaetan Barbet |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes medicine.medical_treatment Immunology Cell Antigen-Presenting Cells Receptor Interferon alpha-beta Biology Lymphocyte Activation Monocytes Article Mice 03 medical and health sciences Interferon medicine Animals Immunology and Allergy B cell Receptors Interleukin-1 Type I B-Lymphocytes Immunity Cellular Microbial Viability Cell Differentiation Inflammasome T-Lymphocytes Helper-Inducer T helper cell Germinal Center Antibodies Neutralizing Immunity Innate Cell biology Adaptor Proteins Vesicular Transport RNA Bacterial 030104 developmental biology Infectious Diseases Cytokine medicine.anatomical_structure TRIF Antibody Formation Bacterial Vaccines Host-Pathogen Interactions Cytokines Biomarkers Signal Transduction medicine.drug |
| Zdroj: | Immunity. 48:584-598.e5 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2018.02.015 |
| Popis: | Summary Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses. The interferon (IFN) and inflammasome pathways downstream of TRIF orchestrated Tfh responses extrinsically to B cells and classical dendritic cells. Instead, CX3CR1+CCR2– monocytes instructed Tfh differentiation through interleukin-1β (IL-1β), a tightly regulated cytokine secreted upon TRIF-dependent IFN licensing of the inflammasome. Hierarchical production of IFN-β and IL-1β dictated Tfh differentiation and elicited the augmented humoral responses characteristic of live vaccines. These findings identify bacterial RNA, an innate signature of microbial viability, as a trigger for Tfh differentiation and suggest new approaches toward vaccine formulations for coordinating augmented Tfh and B cell responses. |
| Databáze: | OpenAIRE |
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