title: Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus.
abstract: Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory-tract infection in infants, the elderly and immunocompromised individuals. Virus-directed cellular immunity elicited by hMPV infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hRSV). In a murine model of acute lower respiratory-tract infection with hMPV, we demonstrate the accumulation of gamma interferon (IFN-gamma)-producing CD8+ T cells in the airways and lungs at day 7 post-infection (p.i.), associated with cytotoxic T lymphocytes (CTLs) directed to an epitope of the M2-1 protein. This CTL immunity was accompanied by increased pulmonary expression of Th1 cytokines IFN-gamma and interleukin (IL)-12 and antiviral cytokines (IFN-beta), as well as chemokines Mip-1alpha, Mip-1beta, Mig, IP-10 and CX3CL1. There was also a moderate increase in Th2-type cytokines IL-4 and IL-10 compared with uninfected mice. At 21 days p.i., a strong CTL response could be recalled from the spleen. A similar pattern of CTL induction to the homologous M2-1 CTL epitope of hRSV, and of cytokine/chemokine induction, was observed following infection with hRSV, highlighting similarities in the cellular immune response to the two related pathogens.
authors.affiliation: Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, and Clinical Medical Virology Centre, University of Queensland, Brisbane, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Herd
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
authors.forename: Robert W
authors.initials: RW
authors.lastname: Tindle
mesh_terms: D000818:Animals; D001835:Body Weight; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000276:immunology / Q000473:pathology; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018184:Paramyxoviridae Infections / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D012137:Respiratory System / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D016207:Cytokines