Macrophage coordination of the interferon lambda immune response

Scott A. Read, Ratna Wijaya, Mehdi Ramezani-Moghadam, Enoch Tay, Steve Schibeci, Christopher Liddle, Vincent W. T. Lam, Lawrence Yuen, Mark W. Douglas, David Booth, Jacob George, Golo Ahlenstiel

Research output: Contribution to journalArticle

3 Citations (Scopus)
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Abstract

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14 + monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.

Original languageEnglish
Article number2674
Pages (from-to)1-16
Number of pages16
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 19 Nov 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • macrophage
  • interferon lambda
  • innate immunity
  • liver
  • Kupffer

Cite this

Read, S. A., Wijaya, R., Ramezani-Moghadam, M., Tay, E., Schibeci, S., Liddle, C., ... Ahlenstiel, G. (2019). Macrophage coordination of the interferon lambda immune response. Frontiers in Immunology, 10, 1-16. [2674]. https://doi.org/10.3389/fimmu.2019.02674