@article{3c6c027392034f18a28c2bd90f7bd228,
title = "Combined TLR4 and TLR9 agonists induce distinct phenotypic changes in innate immunity in vitro and in vivo",
abstract = "Toll-like receptor (TLR)4 and TLR9 agonists, MPL and CpG, are used as adjuvants in vaccines and have been investigated for their combined potential. However, how these two combined agonists regulate transcriptional changes in innate immune cells and cells at the site of vaccination has not been thoroughly investigated. Here, we utilized transcriptomics to investigate how CpG, MPL, and CpG + MPL impact gene expression in dendritic cells (DC) in vitro. Principal component analysis of transcriptional changes after single and combined treatment indicated that CpG, MPL, and CpG + MPL caused distinct gene signatures. CpG + MPL induced antiviral gene expression and activated the interferon regulatory factor pathway. In vitro changes were associated with lower in vivo morbidity upon viral challenge, elevated systemic cytokine protein production, local cytokine mRNA expression, and increased migratory monocyte derived DC populations in the draining lymph node following vaccination with CpG + MPL. This report suggests that CpG + MPL enhances transcription of antiviral and inflammatory genes and increases DC migration.",
keywords = "Adjuvants, Antigen presenting cells, IRF signaling, Innate immunity, NF-κB signaling, TLR4, TLR9, Transcriptomics, Vaccines",
author = "Lampe, {Anna T.} and Puniya, {Bhanwar Lal} and Pannier, {Angela K.} and Tom{\'a}s Helikar and Brown, {Deborah M.}",
note = "Funding Information: DMB and AKP received salary support from NIGMS INBRE P20GM103427 grant. Funding Information: The authors would like to acknowledge the UNMC genomics core for performing RNA-seq experiments and initial analysis of raw data. The University of Nebraska DNA Sequencing Core receives partial support from the National Institute for General Medical Science ( NIGMS ) INBRE - P20GM103427-14 and COBRE - 1P30GM110768-01 grants, as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30CA036727 . This publication{\textquoteright}s contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS . Funding Information: The authors would like to acknowledge the UNMC genomics core for performing RNA-seq experiments and initial analysis of raw data. The University of Nebraska DNA Sequencing Core receives partial support from the National Institute for General Medical Science (NIGMS) INBRE - P20GM103427-14 and COBRE - 1P30GM110768-01 grants, as well as The Fred & Pamela Buffett Cancer Center Support Grant - P30CA036727. This publication's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. The Authors would like to thank Jacey L. Hain, Matthew D. Ballweg, and Kathryn J. Grint, for their contribution to data collection. The authors would also like to thank Dr. Seth Harris and the UNL Veterinary Diagnostic Center for processing and analyzing muscle tissue sections. Funding was provided by: UNL Research Council-Biomedical Seed Grant, Nebraska Research Initiative-Systems Science Seed Grant, the National Institute of General Medical Sciences (R35-GM119770-04), and the National Institutes of Health (1 DP2 EB025760-01). DMB and AKP received salary support from NIGMS INBRE P20GM103427 grant. ATL was supported by NIH T32 Training grant T32GM107001. Funding Information: Funding was provided by: UNL Research Council-Biomedical Seed Grant, Nebraska Research Initiative-Systems Science Seed Grant, the National Institute of General Medical Sciences ( R35-GM119770-04 ), and the National Institutes of Health ( 1 DP2 EB025760-01 ). Funding Information: ATL was supported by NIH T32 Training grant T32GM107001 . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = sep,
doi = "10.1016/j.cellimm.2020.104149",
language = "English (US)",
volume = "355",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
}