NDLI: Human Neuronal Cells Possess Functional Cytoplasmic and Toll-like Receptor-Mediated Innate Immune Pathways Influenced by Phosphatidylinositol-3 Kinase Signaling1

Content Provider	PubMed Central
Author	Peltier, Daniel C. Simms, Allison Farmer, Jocelyn R. Miller, David J.
Abstract	Innate immune pathways are early defense responses important for the immediate control and eventual clearance of many pathogens, where signaling is initiated via pattern recognition receptor-mediated events that occur in a ligand- and cell-type specific manner. Within CNS neurons, innate immune pathways are likely crucial to control pathogens that target these essential yet virtually irreplaceable cells. However, relatively little is known about the induction and regulation of neuronal pattern recognition receptor signaling. In this report, we used human neuronal cell lines and primary rat neuronal cultures to examine pattern recognition receptor expression and function. We found that several innate immune receptor ligands, including Sendai virus, the dsRNA mimetic polyinosinic-polycytidylic acid, and LPS all activated differentiation-dependent neuronal innate immune pathways. Functional genetic analyses revealed that interferon regulatory factor 3-mediated pathways that resulted in IFNβ transcriptional upregulation were activated in cultured human neuronal cells by the pattern recognition receptors TLR3, melanoma differentiated-associated gene 5, or retinoic acid inducible gene I in a ligand-specific manner. Furthermore, genome-wide transcriptional array and targeted genetic and pharmacologic analyses identified PI3K signaling as crucial for the induction of innate immune pathways in neurons. These results indicate that human neuronal cells possess specific and functional pattern recognition receptor pathways essential for the effective induction of innate immune responses, and suggest that neurons can play an active role in defense against neurotropic pathogens.
Related Links	http://dx.doi.org/10.4049/jimmunol.0904133
Ending Page	7021
Page Count	12
Starting Page	7010
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	12
Volume Number	184
Language	English
Publisher Date	2010-06-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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