Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy

Kristin L. Griffiths, Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D. Connell, Kelly D. Moynihan, Jay K. Kolls, Darrell J. Irvine, Maxim N. Artyomov, Javier Rangel-Moreno, Shabaana A. Khader

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4 + T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4 + T-cell responses. In addition, activating endogenous host CD103 + DCs and the CD40-CD40L pathway can similarly induce rapid accumulation of vaccine-induced lung CD4 + T-cell responses and limit early M. tuberculosis growth. Thus, our study provides proof of concept that targeting mucosal DCs can accelerate vaccine-induced T-cell responses on M. tuberculosis infection, and provide insights to overcome bottlenecks in TB vaccine efficacy.

Original languageEnglish
Article number13894
JournalNature communications
Volume7
DOIs
StatePublished - Dec 22 2016

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