TY - JOUR
T1 - Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines
AU - Banchereau, Romain
AU - Baldwin, Nicole
AU - Cepika, Alma Martina
AU - Athale, Shruti
AU - Xue, Yaming
AU - Yu, Chun I.
AU - Metang, Patrick
AU - Cheruku, Abhilasha
AU - Berthier, Isabelle
AU - Gayet, Ingrid
AU - Wang, Yuanyuan
AU - Ohouo, Marina
AU - Snipes, Lu Ann
AU - Xu, Hui
AU - Obermoser, Gerlinde
AU - Blankenship, Derek
AU - Oh, Sangkon
AU - Ramilo, Octavio
AU - Chaussabel, Damien
AU - Banchereau, Jacques
AU - Palucka, Karolina
AU - Pascual, Virginia
N1 - Funding Information:
Financial support for this study was provided by the US National Institutes of Health, grants 5U19AI057234 and 5U19AI089987. We thank all healthy apheresis donors. We also thank Carson Harrod, Ph.D. and members from the genomics, flow cytometry, apheresis core, GMP lab and Luminex core at BIIR for research support.
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014/10/22
Y1 - 2014/10/22
N2 - The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines.
AB - The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines.
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U2 - 10.1038/ncomms6283
DO - 10.1038/ncomms6283
M3 - Article
C2 - 25335753
AN - SCOPUS:84922788803
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 5283
ER -