Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists

Alex C.D. Salyer, Sunil A David

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

An important component of vaccine development is the identification of safe and effective adjuvants. We sought to identify transcriptomal signatures of innate immune stimulating molecules using next-generation RNA sequencing with the goal of being able to utilize such signatures in identifying novel immunostimulatory compounds with adjuvant activity. The CC family of chemokines, particularly CC chemokines 1, 2, 3, 4, 7, 8, 17, 18, 20, and 23, were broadly upregulated by most Toll-like receptor (TLR) and nucleotide-binding domain and leucine-rich repeat–containing receptors (NLR) stimuli. Extracellular receptors such as TLR2, TLR4 and TLR5 induced the transcription of CXC chemokines including CXCL5, CXCL6 and CXCL8, whereas intracellular receptors such as TLR7 and TLR8 upregulated CXC chemokines 11 and 12. Both TLR1/2 and TLR2/6 agonists induced strong chemokine production in human peripheral blood mononuclear cells. Human skeletal muscle cells and fibroblasts respond with chemokine production only to TLR2/6 agonists, but not TLR1/2 agonists, consistent with strong expression of TLR2 and TLR6, but not of TLR1, in fibroblasts. TLR2/6 stimulated fibroblasts demonstrated functional chemotactic responses to human T cell and natural killer cells subsets. The activation of non-hematopoietic, adventitial cells such as fibroblasts and myocytes may contribute.

Original languageEnglish (US)
Pages (from-to)1686-1696
Number of pages11
JournalHuman Vaccines and Immunotherapeutics
Volume14
Issue number7
DOIs
StatePublished - Jul 3 2018

Bibliographical note

Funding Information:
for this project was provided by NIAID Contract HHSN272200900033C. We thank Dr. Mark Sanders and the University of Minnesota Imaging Centers for assistance with the imaging studies. We acknowledge the University Genomics Center, and Dr. Juan Abrahante Llor?ns (University of Minnesota Informatics Institute) for RNASeq and data analysis, respectively. We are grateful to Lauren Fox for her assistance with pilot experiments.

Funding Information:
Funding for this project was provided by NIAID Contract HHSN272200900033C.

Publisher Copyright:
© 2018, © 2018 The Author(s). Published with license by Taylor & Francis.

Keywords

  • Toll-like receptors
  • Type I interferons
  • chemokines
  • chemotaxis
  • transcriptomal profiling
  • vaccine adjuvants

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