PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection

Su Huang, Bibo Zhu, In Su Cheon, Nick P. Goplen, Li Jiang, Ruixuan Zhang, R. Stokes Peebles, Matthias Mack, Mark Kaplan, Andrew H. Limper, Jie Sun

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

Original languageEnglish (US)
Article numbere00030-19
JournalJournal of virology
Volume93
Issue number9
DOIs
StatePublished - May 1 2019

Fingerprint

Peroxisome Proliferator-Activated Receptors
Alveolar Macrophages
Virus Diseases
Respiratory Tract Infections
Pneumonia
macrophages
Influenza A virus
inflammation
lungs
Macrophages
Respiratory Syncytial Virus Infections
infection
viruses
Inflammation
Transcription Factors
tissue repair
Lung
Interferon Type I
transcription factors
Acute Disease

Keywords

  • Alveolar macrophage
  • Inflammation
  • Influenza
  • PPAR-γ
  • Repair
  • RSV

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection. / Huang, Su; Zhu, Bibo; Cheon, In Su; Goplen, Nick P.; Jiang, Li; Zhang, Ruixuan; Stokes Peebles, R.; Mack, Matthias; Kaplan, Mark; Limper, Andrew H.; Sun, Jie.

In: Journal of virology, Vol. 93, No. 9, e00030-19, 01.05.2019.

Research output: Contribution to journalArticle

Huang, S, Zhu, B, Cheon, IS, Goplen, NP, Jiang, L, Zhang, R, Stokes Peebles, R, Mack, M, Kaplan, M, Limper, AH & Sun, J 2019, 'PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection', Journal of virology, vol. 93, no. 9, e00030-19. https://doi.org/10.1128/JVI.00030-19
Huang, Su ; Zhu, Bibo ; Cheon, In Su ; Goplen, Nick P. ; Jiang, Li ; Zhang, Ruixuan ; Stokes Peebles, R. ; Mack, Matthias ; Kaplan, Mark ; Limper, Andrew H. ; Sun, Jie. / PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection. In: Journal of virology. 2019 ; Vol. 93, No. 9.
@article{f7336697b0634f2b9d87c252ed063417,
title = "PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection",
abstract = "Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.",
keywords = "Alveolar macrophage, Inflammation, Influenza, PPAR-γ, Repair, RSV",
author = "Su Huang and Bibo Zhu and Cheon, {In Su} and Goplen, {Nick P.} and Li Jiang and Ruixuan Zhang and {Stokes Peebles}, R. and Matthias Mack and Mark Kaplan and Limper, {Andrew H.} and Jie Sun",
year = "2019",
month = "5",
day = "1",
doi = "10.1128/JVI.00030-19",
language = "English (US)",
volume = "93",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection

AU - Huang, Su

AU - Zhu, Bibo

AU - Cheon, In Su

AU - Goplen, Nick P.

AU - Jiang, Li

AU - Zhang, Ruixuan

AU - Stokes Peebles, R.

AU - Mack, Matthias

AU - Kaplan, Mark

AU - Limper, Andrew H.

AU - Sun, Jie

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

AB - Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

KW - Alveolar macrophage

KW - Inflammation

KW - Influenza

KW - PPAR-γ

KW - Repair

KW - RSV

UR - http://www.scopus.com/inward/record.url?scp=85065049367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065049367&partnerID=8YFLogxK

U2 - 10.1128/JVI.00030-19

DO - 10.1128/JVI.00030-19

M3 - Article

C2 - 30787149

AN - SCOPUS:85065049367

VL - 93

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

M1 - e00030-19

ER -