Cargando…
Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection
Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to imm...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355693/ https://www.ncbi.nlm.nih.gov/pubmed/34394082 http://dx.doi.org/10.3389/fimmu.2021.688294 |
_version_ | 1783736811342790656 |
---|---|
author | Zhang, Wen Fu, Zhendong Yin, Hongyan Han, Qingbing Fan, Wenhui Wang, Fangkun Shang, Yingli |
author_facet | Zhang, Wen Fu, Zhendong Yin, Hongyan Han, Qingbing Fan, Wenhui Wang, Fangkun Shang, Yingli |
author_sort | Zhang, Wen |
collection | PubMed |
description | Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis. |
format | Online Article Text |
id | pubmed-8355693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83556932021-08-12 Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection Zhang, Wen Fu, Zhendong Yin, Hongyan Han, Qingbing Fan, Wenhui Wang, Fangkun Shang, Yingli Front Immunol Immunology Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8355693/ /pubmed/34394082 http://dx.doi.org/10.3389/fimmu.2021.688294 Text en Copyright © 2021 Zhang, Fu, Yin, Han, Fan, Wang and Shang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhang, Wen Fu, Zhendong Yin, Hongyan Han, Qingbing Fan, Wenhui Wang, Fangkun Shang, Yingli Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title | Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title_full | Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title_fullStr | Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title_full_unstemmed | Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title_short | Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection |
title_sort | macrophage polarization modulated by porcine circovirus type 2 facilitates bacterial coinfection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355693/ https://www.ncbi.nlm.nih.gov/pubmed/34394082 http://dx.doi.org/10.3389/fimmu.2021.688294 |
work_keys_str_mv | AT zhangwen macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT fuzhendong macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT yinhongyan macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT hanqingbing macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT fanwenhui macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT wangfangkun macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection AT shangyingli macrophagepolarizationmodulatedbyporcinecircovirustype2facilitatesbacterialcoinfection |