Toll-like receptor 3 has no critical role during early immune response of human monocyte-derived dendritic cells after infection with the human cytomegalovirus strain TB40E.
Toll-like receptors (TLRs) recognize an increasingly broad range of pathogens, thus demonstrating the importance of these pattern-recognition receptors (PRRs) in host defense. Here, the role of TLR3 in the interaction of monocyte-derived dendritic cells (moDCs) with human cytomegalovirus (HCMV) was investigated by using the TB40E strain, which actively replicates in moDCs. Microarray analysis and quantitative real-time PCR revealed that TB40E infection of moDCs led to changes in the gene expression pattern. A variety of proinflammatory cytokines and chemokines (CXCL10, CXCL11, and CCL5), TLR3, and genes whose products function downstream of the TLR3 signaling pathway (e.g., IFN-alpha and IFN-beta) were significantly upregulated. By silencing TLR3 expression with short interfering RNA (siRNA), and subsequent stimulation with TLR3 ligand poly I:C, expression of IFN-beta was markedly reduced compared to cells transfected with a non-silencing control siRNA. However, expression of IFN-beta induced by HCMV was not diminished when TLR3 was silenced first. Thus the early HCMV-triggered immune response of human moDCs appears to be independent of TLR3 signaling.
Mezger
Markus
M
Julius-Maximilians-Universität Würzburg , Medizinische Klinik & Poliklinik II, Eberhard-Karls-Universität Tuebingen, Tübingen, Germany .
Bonin
Michael
M
Kessler
Tobias
T
Gebhardt
Florian
F
Einsele
Hermann
H
Loeffler
Juergen
J
D002454:Cell Differentiation; D002478:Cells, Cultured / Q000821:virology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000166:cytology; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007231:Infant, Newborn; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009000:Monocytes / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D011070:Poly I-C / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D034741:RNA, Small Interfering; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C