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Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment

Menzel, Mandy LU ; Kosinski, Joakim ; Uller, Lena LU and Akbarshahi, Hamid LU (2019) In Scientific Reports 9(1).
Abstract

Macrophages play an important role in asthma pathogenesis both in the inflammatory and resolution phase of the disease. Macrophages can acquire different polarisation states dependent on their microenvironment. It is yet unclear through which mechanism the microenvironment affects the anti-viral response in macrophages. We hypothesized that the macrophage microenvironment regulates rhinovirus-induced IFNβ expression. Murine bone marrow-derived monocytes and human differentiated THP-1 cells were stimulated with M-CSF or GM-CSF and IFNγ or IL-4/IL-13, respectively, to mimic a Th1 or Th2 environment. Macrophages were infected with rhinovirus and gene and protein levels of IFNβ and pattern recognition receptor expression were measured. In... (More)

Macrophages play an important role in asthma pathogenesis both in the inflammatory and resolution phase of the disease. Macrophages can acquire different polarisation states dependent on their microenvironment. It is yet unclear through which mechanism the microenvironment affects the anti-viral response in macrophages. We hypothesized that the macrophage microenvironment regulates rhinovirus-induced IFNβ expression. Murine bone marrow-derived monocytes and human differentiated THP-1 cells were stimulated with M-CSF or GM-CSF and IFNγ or IL-4/IL-13, respectively, to mimic a Th1 or Th2 environment. Macrophages were infected with rhinovirus and gene and protein levels of IFNβ and pattern recognition receptor expression were measured. In subsequent experiments an IκB kinase inhibitor was used to study the involvement of NFκB. Both murine and human M1-like macrophages exhibited higher levels of IFNβ and pattern recognition receptors after rhinovirus infection than M2-like macrophages. Blockage of NFκB resulted in a lower expression of rhinovirus-induced IFNβ in human M1-like macrophages while inducing a higher expression in M2-like macrophages, suggesting that the interferon response towards viral infection was mediated by NFκB. These findings could contribute to a better understanding of mechanisms causing reduced anti-viral responses at viral-induced exacerbations in asthma.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
13394
publisher
Nature Publishing Group
external identifiers
  • pmid:31527772
  • scopus:85072278394
ISSN
2045-2322
DOI
10.1038/s41598-019-50034-1
language
English
LU publication?
yes
id
134b3185-acd2-48fc-877d-d1752cdd2099
date added to LUP
2019-09-30 14:47:42
date last changed
2024-07-10 03:41:51
@article{134b3185-acd2-48fc-877d-d1752cdd2099,
  abstract     = {{<p>Macrophages play an important role in asthma pathogenesis both in the inflammatory and resolution phase of the disease. Macrophages can acquire different polarisation states dependent on their microenvironment. It is yet unclear through which mechanism the microenvironment affects the anti-viral response in macrophages. We hypothesized that the macrophage microenvironment regulates rhinovirus-induced IFNβ expression. Murine bone marrow-derived monocytes and human differentiated THP-1 cells were stimulated with M-CSF or GM-CSF and IFNγ or IL-4/IL-13, respectively, to mimic a Th1 or Th2 environment. Macrophages were infected with rhinovirus and gene and protein levels of IFNβ and pattern recognition receptor expression were measured. In subsequent experiments an IκB kinase inhibitor was used to study the involvement of NFκB. Both murine and human M1-like macrophages exhibited higher levels of IFNβ and pattern recognition receptors after rhinovirus infection than M2-like macrophages. Blockage of NFκB resulted in a lower expression of rhinovirus-induced IFNβ in human M1-like macrophages while inducing a higher expression in M2-like macrophages, suggesting that the interferon response towards viral infection was mediated by NFκB. These findings could contribute to a better understanding of mechanisms causing reduced anti-viral responses at viral-induced exacerbations in asthma.</p>}},
  author       = {{Menzel, Mandy and Kosinski, Joakim and Uller, Lena and Akbarshahi, Hamid}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment}},
  url          = {{http://dx.doi.org/10.1038/s41598-019-50034-1}},
  doi          = {{10.1038/s41598-019-50034-1}},
  volume       = {{9}},
  year         = {{2019}},
}