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Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune-Responses

Jardin A. Leleux, Pallab Pradhan, Krishnendu Roy
doi: https://doi.org/10.1101/076935
Jardin A. Leleux
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory The Parker H. Petit Institute for Bioengineering and Biosciences Center for ImmunoEngineering at Georgia Tech Georgia Institute of Technology, Atlanta, GA, 30332
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Pallab Pradhan
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory The Parker H. Petit Institute for Bioengineering and Biosciences Center for ImmunoEngineering at Georgia Tech Georgia Institute of Technology, Atlanta, GA, 30332
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Krishnendu Roy
The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory The Parker H. Petit Institute for Bioengineering and Biosciences Center for ImmunoEngineering at Georgia Tech Georgia Institute of Technology, Atlanta, GA, 30332
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  • For correspondence: krish.roy@gatech.edu
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Abstract

It is currently unknown whether and how mammalian pathogen-recognition receptors (PRR) respond to biophysical patterns of pathogen-associated molecular danger-signals. Using synthetic pathogen-like particles (PLPs) that mimic physical properties of bacteria or large-viruses, we have discovered that the quality and quantity of Toll-like-receptor-9 (TLR9)-signaling by CpG in mouse dendritic cells (mDC) is uniquely dependent on biophysical attributes, specifically the surface-density of CpG and size of the presenting PLP. These physical patterns control DC-programming by regulating kinetics and magnitude of MyD88-IRAK4 signaling, NFκB-driven responses, and STAT3 phosphorylation, which in turn controls differential T cell responses and in vivo immune-polarization, especially T-helper 1 (Th1) versus T-helper 2 (Th2) antibody responses. Our findings suggest that innate immune cells can sense and respond not only to molecular, but also pathogen-associated physical patterns (PAPPs), broadening the tools for modulating immunity, helping to better understand innate response mechanisms to pathogens and develop new and improved vaccines.

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Posted September 23, 2016.
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Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune-Responses
Jardin A. Leleux, Pallab Pradhan, Krishnendu Roy
bioRxiv 076935; doi: https://doi.org/10.1101/076935
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Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune-Responses
Jardin A. Leleux, Pallab Pradhan, Krishnendu Roy
bioRxiv 076935; doi: https://doi.org/10.1101/076935

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