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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Wen, Fu, Zhendong, Yin, Hongyan, Han, Qingbing, Fan, Wenhui, Wang, Fangkun, Shang, Yingli
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