title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis.
abstract: Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children.
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Jostein
authors.initials: J
authors.lastname: Malmo
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.|Childhood Airway Infections Research Group, Children's Clinic, St. Olav's Hospital, Trondheim University Hospital, 7491 Trondheim, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Moe
authors.affiliation: Childhood Airway Infections Research Group, Department of Medical Microbiology, St. Olav's Hospital, Trondheim University Hospital, 7491 Trondheim, Norway.
authors.forename: Sidsel
authors.initials: S
authors.lastname: Krokstad
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Liv
authors.initials: L
authors.lastname: Ryan
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Simon
authors.initials: S
authors.lastname: Loevenich
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Ingvild B
authors.initials: IB
authors.lastname: Johnsen
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.|Childhood Airway Infections Research Group, Department of Medical Microbiology, St. Olav's Hospital, Trondheim University Hospital, 7491 Trondheim, Norway.
authors.forename: Svein Arne
authors.initials: SA
authors.lastname: Nordbø
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.|Childhood Airway Infections Research Group, Children's Clinic, St. Olav's Hospital, Trondheim University Hospital, 7491 Trondheim, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Døllner
authors.affiliation: Childhood Airway Infections Research Group, Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Marit W
authors.initials: MW
authors.lastname: Anthonsen
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007223:Infant; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008297:Male; D029121:Metapneumovirus / Q000187:drug effects / Q000472:pathogenicity*; D009305:Nasopharynx / Q000473:pathology / Q000821:virology; D018184:Paramyxoviridae Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D058847:Inflammasomes; D007372:Interferons