CpG oligodeoxynucleotides stimulate IFN-gamma-inducible protein-10 production in human B cells.
Several classes of CpG oligodeoxynucleotides (ODNs) with different immune stimulatory profiles were recently identified: the A-, B- and C-classes. In this study, we investigated the CpG-dependent stimulation of IFN-gamma-inducible protein 10 (IP-10 or CXCL10) in different human immune cell types. CpG ODNs induced IP-10 in monocytes, pDCs and in B cells. Purified B cells as well as RPMI 8226 cells responded to CpG stimulation by IP-10 production. Treatment with exogenous IFN-alpha2b sensitized PBMCs, purified B cells as well as RPMI 8226 cells to respond more efficiently to stimulation with CpG ODNs by IP-10 production. IP-10 signaling could be directly stimulated via TLR9 in CpG-unresponsive HEK293 cells transfected with human TLR9 and an IP-10 reporter construct. Therefore, CpG-mediated IP-10 production is stimulated through IFN-alpha in cells that express the IFN-alpha receptor, a second pathway for IP-10 induction exists in TLR9-expressing B cells and pDCs where IP-10 is stimulated directly upon CpG-mediated TLR9 signaling. Our data provide a better understanding of the mechanisms through which CpG ODNs induce efficient Th1 responses.
Vollmer
Jörg
J
Coley Pharmaceutical GmbH, Langenfeld, Germany.
Jurk
Marion
M
Samulowitz
Ulrike
U
Lipford
Grayson
G
Forsbach
Alexandra
A
Wüllner
Meike
M
Tluk
Sybille
S
Hartmann
Hanna
H
Kritzler
Andrea
A
Müller
Christian
C
Schetter
Christian
C
Krieg
Arthur M
AM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis*; D018899:CpG Islands / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000145:classification / Q000494:pharmacology*; D053633:Receptor, Interferon alpha-beta; D011956:Receptors, Cell Surface / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014162:Transfection
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D017931:DNA Primers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma