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Human Metapneumovirus Glycoprotein G Inhibits TLR4-Dependent Signaling in Monocyte-Derived Dendritic Cells
| Content Provider | Scilit |
|---|---|
| Author | Kolli, Deepthi Bao, Xiaoyong Liu, Tianshuang Hong, Chao Wang, Tian Garofalo, Roberto P. Casola, Antonella |
| Copyright Year | 2011 |
| Description | Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory infections in children and adults. Recent work from our group demonstrated that hMPV G glycoprotein is an important virulence factor, responsible for inhibiting innate immune responses in airway epithelial cells. Myeloid dendritic cells (DCs) are potent APCs and play a major role in initiating and modulating the innate and adaptive immune responses. In this study, we found that TLR4 plays a major role in hMPV-induced activation of monocyte-derived DCs (moDCs), as downregulation of its expression by small interfering RNA significantly blocked hMPV-induced chemokine and type I IFN expression. Similar results were found in bone marrow-derived DCs from TLR4-deficient mice. moDCs infected with a virus lacking G protein expression produced higher levels of cytokines and chemokines compared with cells infected with wild-type virus, suggesting that G protein plays an inhibitory role in viral-induced cellular responses. Specifically, G protein affects TLR4-dependent signaling, as infection of moDCs with recombinant hMPV lacking G protein inhibited LPS-induced production of cytokine and chemokines significantly less than did wild-type virus, and treatment of moDCs with purified G protein resulted in a similar inhibition of LPS-dependent signaling. Our results demonstrate that hMPV G protein plays an important role in inhibiting host innate immune responses, likely affecting adaptive responses too. |
| Ending Page | 54 |
| Page Count | 8 |
| Starting Page | 47 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1002589 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/187/1/47.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 1 |
| Volume Number | 187 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2011-07-01 |
| Access Restriction | Open |
| Subject Keyword | Innate Immune Small Interfering Rna Bone Marrow Tlr4 Dependent Signaling Demonstrate That Hmpv |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
