Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines

NATURE COMMUNICATIONS | ARTICLE OPEN

• Romain Banchereau,
• Nicole Baldwin,
• Alma-Martina Cepika,
• Shruti Athale,
• Yaming Xue,
• Chun I Yu,
• Patrick Metang,
• Abhilasha Cheruku,
• Isabelle Berthier,
• Ingrid Gayet,
• Yuanyuan Wang,
• Marina Ohouo,
• LuAnn Snipes,
• Hui Xu,
• Gerlinde Obermoser,
• Derek Blankenship,
• Sangkon Oh,
• Octavio Ramilo,
• Damien Chaussabel,
• Jacques Banchereau
• et al.

Nature Communications

 

5,

 

Article number:

 

5283

 

doi:10.1038/ncomms6283

Received

 

02 June 2014 

Accepted

 

16 September 2014 

Published

 

22 October 2014

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Abstract

• Abstract• 
• Introduction• 
• Results• 
• Discussion• 
• Methods• 
• Additional information• 
• Accession codes•
• References• 
• Acknowledgements• 
• Author information• 
• Supplementary information

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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