Jens Christian Jensenius

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

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DOI

  • Mitchell R White, 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • ,
  • Shweta Tripathi, 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • ,
  • Anamika Verma, 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • ,
  • Paul Kingma, 2 University of Cincinnati School of Medicine, Cincinnati, OH, USA.
  • ,
  • Kazue Takahashi, 3 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • ,
  • Jens Jensenius
  • Steffen Thiel
  • Guangshun Wang, 5 Department of Pathology and Microbiology, Nebraska Medical Center, Omaha, NE, USA.
  • ,
  • Erika C Crouch, 6 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • ,
  • Kevan L Hartshorn, 1 Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

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.

Original languageEnglish
JournalInnate Immunity
Volume23
Issue1
Pages (from-to)77-88
Number of pages12
ISSN1753-4259
DOIs
Publication statusPublished - Jan 2017

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