title: Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus.
abstract: Dendritic cells (DCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract. Human metapneumovirus (hMPV) is a recently identified pathogen and like its better known relative, respiratory syncytial virus (RSV), has been increasingly recognized as a major cause of respiratory morbidity in infants and in elderly persons. In the present study, we examined susceptibility as well as cellular responses of human DCs to hMPV compared with RSV. Monocyte-derived DCs (moDCs) were susceptible to infection by both viruses, but only RSV was able to induce a productive infection with release of viral progeny. Despite the fact that viral infection resulted in phenotypic maturation of moDCs, as shown by the upregulation of cell surface markers and antigen-presenting molecules (MHC I and II, CD80, CD83, CD86, CD38), RSV-infected moDCs showed a severely impaired capacity to stimulate CD4+ T cell proliferation. Compared with hMPV, RSV was a more potent inducer of inflammatory and immunomodulatory cytokines, including TNF-alpha, IL-6, IL-1beta, IL-10, and IL-12p70 in both moDCs and plasmacytoid dendritic cells (pDCs). On the other hand, hMPV, but not RSV, was able to trigger production of IFN-alpha by moDCs, while both viruses strongly induced IFN-alpha in pDCs. Finally, both viruses strikingly suppressed IFN-alpha production by moDCs or pDCs stimulated with synthetic dsRNA and CpG-ODN, respectively. The findings provide novel evidence that RSV and hMPV differentially activate human DCs and may use distinct mechanisms to interfere with the host innate and adaptive immune responses.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0369, USA.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Guerrero-Plata
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: LeAnne
authors.initials: L
authors.lastname: Spetch
authors.forename: Mark E
authors.initials: ME
authors.lastname: Peeples
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D029121:Metapneumovirus / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D012136:Respiratory Syncytial Viruses / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D016898:Interferon-alpha