Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level, IL-12 Secretion by Dendritic Cells

Gary K. Koski, Katalin Karikó, Shuwen Xu, Drew Weissman, Peter A Cohen, Brian J. Czerniecki

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3′-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3′-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-γhigh IL-5low Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.

Original languageEnglish (US)
Pages (from-to)3989-3993
Number of pages5
JournalJournal of Immunology
Volume172
Issue number7
StatePublished - Apr 1 2004
Externally publishedYes

Fingerprint

Bacterial RNA
Interleukin-12
Dendritic Cells
Immune System
RNA
Messenger RNA
Bacterial Structures
Poly U
Polyadenylation
Monocytes
Vaccines
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Cutting Edge : Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level, IL-12 Secretion by Dendritic Cells. / Koski, Gary K.; Karikó, Katalin; Xu, Shuwen; Weissman, Drew; Cohen, Peter A; Czerniecki, Brian J.

In: Journal of Immunology, Vol. 172, No. 7, 01.04.2004, p. 3989-3993.

Research output: Contribution to journalArticle

@article{9b271a2add144b59ab1770187b7f3225,
title = "Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level, IL-12 Secretion by Dendritic Cells",
abstract = "RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3′-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3′-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-γhigh IL-5low Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.",
author = "Koski, {Gary K.} and Katalin Karik{\'o} and Shuwen Xu and Drew Weissman and Cohen, {Peter A} and Czerniecki, {Brian J.}",
year = "2004",
month = "4",
day = "1",
language = "English (US)",
volume = "172",
pages = "3989--3993",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Cutting Edge

T2 - Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level, IL-12 Secretion by Dendritic Cells

AU - Koski, Gary K.

AU - Karikó, Katalin

AU - Xu, Shuwen

AU - Weissman, Drew

AU - Cohen, Peter A

AU - Czerniecki, Brian J.

PY - 2004/4/1

Y1 - 2004/4/1

N2 - RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3′-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3′-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-γhigh IL-5low Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.

AB - RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3′-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3′-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-γhigh IL-5low Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.

UR - http://www.scopus.com/inward/record.url?scp=1642268316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642268316&partnerID=8YFLogxK

M3 - Article

C2 - 15034009

AN - SCOPUS:1642268316

VL - 172

SP - 3989

EP - 3993

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -