@article{9161d9d183ee411194d0c0626fa88363,
title = "Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy",
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.",
author = "Griffiths, {Kristin L.} and Mushtaq Ahmed and Shibali Das and Radha Gopal and William Horne and Connell, {Terry D.} and Moynihan, {Kelly D.} and Kolls, {Jay K.} and Irvine, {Darrell J.} and Artyomov, {Maxim N.} and Javier Rangel-Moreno and Khader, {Shabaana A.}",
note = "Funding Information: This work was supported by Washington University in St Louis, National Institute of Health grant HL105427, AI127172 to S.A.K., by the Ragon Institute of MGH, MIT, and Harvard and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies (contract W911NF-13-D-0001) to D.J.I., American Lung Association Senior Research Training Fellowship RT-30592, Department of Molecular Microbiology, Washington University St Louis, and Alexander and Gertrude Berg Fellowship to K.L.G. J.R.-M. was supported by funds of the Department of Medicine, University of Rochester, and U19 AI91036. Publisher Copyright: {\textcopyright} The Author(s) 2016.",
year = "2016",
month = dec,
day = "22",
doi = "10.1038/ncomms13894",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
}