title: Paramyxovirus infection regulates T cell responses by BDCA-1+ and BDCA-3+ myeloid dendritic cells.
abstract: Respiratory syncytial virus (RSV) and human Metapneumovirus (hMPV), viruses belonging to the family Paramyxoviridae, are the most important causes of lower respiratory tract infection in young children. Infections with RSV and hMPV are clinically indistinguishable, and both RSV and hMPV infection have been associated with aberrant adaptive immune responses. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping adaptive immune responses during infection; however, few studies have examined how interactions of RSV and hMPV with individual mDC subsets (BDCA-1(+) and BDCA-3(+) mDCs) affect the outcome of anti-viral responses. To determine whether RSV and hMPV induce virus-specific responses from each subset, we examined co-stimulatory molecules and cytokines expressed by BDCA-1(+) and BDCA-3(+) mDCs isolated from peripheral blood after infection with hMPV and RSV, and examined their ability to stimulate T cell proliferation and differentiation. Our data show that RSV and hMPV induce virus-specific and subset-specific patterns of co-stimulatory molecule and cytokine expression. RSV, but not hMPV, impaired the capacity of infected mDCs to stimulate T cell proliferation. Whereas hMPV-infected BDCA-1(+) and BDCA-3(+) mDCs induced expansion of Th17 cells, in response to RSV, BDCA-1(+) mDCs induced expansion of Th1 cells and BDCA-3(+) mDCs induced expansion of Th2 cells and Tregs. These results demonstrate a virus-specific and subset-specific effect of RSV and hMPV infection on mDC function, suggesting that these viruses may induce different adaptive immune responses.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Meera R
authors.initials: MR
authors.lastname: Gupta
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Kolli
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Molteni
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D018184:Paramyxoviridae Infections / Q000276:immunology*; D018180:Thrombomodulin
chemical_list: D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins; D016898:Interferon-alpha; C546931:THBD protein, human; D018180:Thrombomodulin