Type I interferon signaling regulates Ly6Chi monocytes and neutrophils during acute viral pneumonia in mice

Sang Uk Seo, Hyung Joon Kwon, Hyun Jeong Ko, Young Ho Byun, Baik Lin Seong, Satoshi Uematsu, Shizuo Akira, Mi Na Kweon

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1-/-) mice develop significant defects in the infiltration of Ly6Chi monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6Chi monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6Cint monocytes of Ifnar1-/- mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1-/- mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6Chi monocytes. By using BM chimeric mice (WT BM into Ifnar1-/- and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6Chi monocytes. Of note, WT BM reconstituted Ifnar1-/- chimeric mice with increased numbers of Ly6Chi monocytes survived longer than influenza-infected Ifnar1-/- mice. In contrast, WT mice that received Ifnar1-/- BM cells with alternative Ly6Cint monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung.

Original languageEnglish
Article numbere1001304
JournalPLoS Pathogens
Volume7
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

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Viral Pneumonia
Interferon Type I
Monocytes
Neutrophils
Human Influenza
Bone Marrow Cells
Bone Marrow
Lung
Blocking Antibodies
Infection Control
Hematopoietic Stem Cells
Infection
Knockout Mice
Homeostasis
Inflammation

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Seo, Sang Uk ; Kwon, Hyung Joon ; Ko, Hyun Jeong ; Byun, Young Ho ; Seong, Baik Lin ; Uematsu, Satoshi ; Akira, Shizuo ; Kweon, Mi Na. / Type I interferon signaling regulates Ly6Chi monocytes and neutrophils during acute viral pneumonia in mice. In: PLoS Pathogens. 2011 ; Vol. 7, No. 2.
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Type I interferon signaling regulates Ly6Chi monocytes and neutrophils during acute viral pneumonia in mice. / Seo, Sang Uk; Kwon, Hyung Joon; Ko, Hyun Jeong; Byun, Young Ho; Seong, Baik Lin; Uematsu, Satoshi; Akira, Shizuo; Kweon, Mi Na.

In: PLoS Pathogens, Vol. 7, No. 2, e1001304, 01.02.2011.

Research output: Contribution to journalArticle

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