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

10 Citations (Scopus)

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

Fingerprint

Collectins
Influenza A virus
Monocytes
Pulmonary Surfactant-Associated Protein D
Cytokines
Viruses
Mannose-Binding Lectin
Pandemics
Proteins
Inflammation Mediators
Virus Diseases
Virus Replication
ficolin
Lectins
Antiviral Agents

Keywords

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

ASJC Scopus subject areas

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

Cite this

White, M. R., Tripathi, S., Verma, A., Kingma, P., Takahashi, K., Jensenius, J., ... 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

Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production. / White, Mitchell R.; Tripathi, Shweta; Verma, Anamika; Kingma, Paul; Takahashi, Kazue; Jensenius, Jens; Thiel, Steffen; Wang, Guangshun; Crouch, Erika C.; Hartshorn, Kevan L.

In: Innate Immunity, Vol. 23, No. 1, 01.01.2017, p. 77-88.

Research output: Contribution to journalArticle

White, MR, Tripathi, S, Verma, A, Kingma, P, Takahashi, K, Jensenius, J, Thiel, S, Wang, G, Crouch, EC & Hartshorn, KL 2017, 'Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production', Innate Immunity, vol. 23, no. 1, pp. 77-88. https://doi.org/10.1177/1753425916678470
White, Mitchell R. ; Tripathi, Shweta ; Verma, Anamika ; Kingma, Paul ; Takahashi, Kazue ; Jensenius, Jens ; Thiel, Steffen ; Wang, Guangshun ; Crouch, Erika C. ; Hartshorn, Kevan L. / Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production. In: Innate Immunity. 2017 ; Vol. 23, No. 1. pp. 77-88.
@article{8c8c19ba6069468fa5c5b72be06c83f3,
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.",
keywords = "Neutrophil, TNF-α, antimicrobial peptide, pandemic, phagocyte",
author = "White, {Mitchell R.} and Shweta Tripathi and Anamika Verma and Paul Kingma and Kazue Takahashi and Jens Jensenius and Steffen Thiel and Guangshun Wang and Crouch, {Erika C.} and Hartshorn, {Kevan L.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1177/1753425916678470",
language = "English (US)",
volume = "23",
pages = "77--88",
journal = "Innate Immunity",
issn = "1753-4259",
publisher = "SAGE Publications Ltd",
number = "1",

}

TY - JOUR

T1 - Collectins, H-ficolin and LL-37 reduce influence viral replication in human monocytes and modulate virus-induced cytokine production

AU - White, Mitchell R.

AU - Tripathi, Shweta

AU - Verma, Anamika

AU - Kingma, Paul

AU - Takahashi, Kazue

AU - Jensenius, Jens

AU - Thiel, Steffen

AU - Wang, Guangshun

AU - Crouch, Erika C.

AU - Hartshorn, Kevan L.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Neutrophil

KW - TNF-α

KW - antimicrobial peptide

KW - pandemic

KW - phagocyte

UR - http://www.scopus.com/inward/record.url?scp=85006716733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006716733&partnerID=8YFLogxK

U2 - 10.1177/1753425916678470

DO - 10.1177/1753425916678470

M3 - Article

C2 - 27856789

AN - SCOPUS:85006716733

VL - 23

SP - 77

EP - 88

JO - Innate Immunity

JF - Innate Immunity

SN - 1753-4259

IS - 1

ER -