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

Mitchell R. White, Shweta Tripathi, Anamika Verma, Paul Kingma, Kazue Takahashi, Jens Jensenius, Steffen Thiel, Guangshun Wang, Erika C. Crouch, Kevan L. Hartshorn

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)77-88
Number of pages12
JournalInnate Immunity
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Neutrophil
  • TNF-α
  • antimicrobial peptide
  • pandemic
  • phagocyte

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production'. Together they form a unique fingerprint.

  • Cite this

    White, M. R., Tripathi, S., Verma, A., Kingma, P., Takahashi, K., Jensenius, J., Thiel, S., Wang, G., Crouch, E. C., & Hartshorn, K. L. (2017). Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production. Innate Immunity, 23(1), 77-88. https://doi.org/10.1177/1753425916678470