title: Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production.
abstract: Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin also increased viral uptake by the cells, while LL-37 did not. H-ficolin was able to inhibit replication of the 2009 pandemic H1N1 strain (Cal09) in monocytes, but SP-D and LL-37 had significantly fewer inhibitory effects on this strain than on seasonal IAV. All of these proteins reduced IAV-induced TNF-α production, even in instances when viral replication was not reduced. We used modified recombinant versions of SP-D, MBL and ficolin to elucidate mechanisms through which these proteins alter monocyte interactions with IAV. We demonstrate the importance of the multimeric structure, and of binding properties of the lectin domain, in mediating antiviral and opsonic activity of the proteins. Hence, soluble inhibitors present in airway lining fluid may aid clearance of IAV by promoting monocyte uptake of the virus, while reducing viral replication and virus-induced TNF-α responses in these cells. However, SP-D and LL-37 have reduced ability to inhibit replication of pandemic IAV in monocytes.
authors.affiliation: 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.affiliation: 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Anamika
authors.initials: A
authors.lastname: Verma
authors.affiliation: 2 University of Cincinnati School of Medicine, Cincinnati, OH, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Kingma
authors.affiliation: 3 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: 4 Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Jensenius
authors.affiliation: 4 Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.affiliation: 5 Department of Pathology and Microbiology, Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Guangshun
authors.initials: G
authors.lastname: Wang
authors.affiliation: 6 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.affiliation: 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002478:Cells, Cultured; D037222:Collectins / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000821:virology; D010587:Phagocytosis / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D015202:Protein Engineering; D055503:Protein Multimerization / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D037222:Collectins; C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha; D054804:Cathelicidins
keywords: Neutrophil; TNF-α; antimicrobial peptide; pandemic; phagocyte