Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • March 13, 2018

Research

keywords

  • Antibody Formation
  • B-Lymphocytes
  • Lymphocyte Activation
  • Microbial Viability
  • RNA, Bacterial
  • T-Lymphocytes, Helper-Inducer

Identity

PubMed Central ID

  • PMC5924674

Scopus Document Identifier

  • 85043350816

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2018.02.015

PubMed ID

  • 29548673

Additional Document Info

volume

  • 48

issue

  • 3