Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells.
We examined the gene expression and regulation of type III human interferon (IFN), IFN-lambda, in human neuronal cells. Human neuronal cells expressed endogenous IFN-lambda1 but not IFN-lambda2/3. Upon the activation of Toll-like receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic polyribocytidylic acid (PolyI:C), both IFN-lambda1 and IFN-lambda2/3 expression was significantly induced. The activation of TLR-3 also exhibited antiviral activity against pseudotyped human immunodeficiency virus (HIV)-1 infection of the neuronal cells. Human neuronal cells also expressed functional IFN-lambda receptor complex, interleukin-28 receptor alpha subunit (IL-28Ralpha) and IL-10Rbeta, as evidenced by the observations that exogenous IFN-lambda treatment inhibited pseudotyped HIV-1 infection of the neuronal cells and induced the expression of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that there is intracellular expression and regulation of IFN-lambda in human neuronal cells, which may have an important role in the innate neuronal protection against viral infections in the CNS.
Zhou
L
L
Division of Allergy and Immunology, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wang
X
X
Wang
Y J
YJ
Zhou
Y
Y
Hu
S
S
Ye
L
L
Hou
W
W
Li
H
H
Ho
W Z
WZ
D000071478:APOBEC Deaminases; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000378:metabolism*; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D007369:Interferon Inducers; D053710:Interleukin-10 Receptor beta Subunit; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D051196:Toll-Like Receptor 3; C471046:interleukin 28alpha receptor; D014212:Tretinoin; D007372:Interferons; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase; D011070:Poly I-C