Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair

ABSTRACT Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation re...

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Autores principales:	Ali Zaid, Kothila Tharmarajah, Helen Mostafavi, Joseph R. Freitas, Kuo-Ching Sheng, Suan-Sin Foo, Weiqiang Chen, Jelena Vider, Xiang Liu, Nicholas P. West, Lara J. Herrero, Adam Taylor, Laura K. Mackay, Daniel R. Getts, Nicholas J. C. King, Suresh Mahalingam
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	inflammation macrophages microparticles myositis Ross River virus tissue repair Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f8569b9c0cc8402c8c2be12438a0281e
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spelling	oai:doaj.org-article:f8569b9c0cc8402c8c2be12438a0281e2021-11-15T15:57:01ZModulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair10.1128/mBio.03353-192150-7511https://doaj.org/article/f8569b9c0cc8402c8c2be12438a0281e2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03353-19https://doaj.org/toc/2150-7511ABSTRACT Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11bhi Ly6Chi inflammatory monocytes and followed by the establishment of a CD11bhi Ly6Clo CX3CR1+ macrophage population in the muscle upon recovery. Selective modulation of CD11bhi Ly6Chi monocyte migration to infected muscle using immune-modifying microparticles (IMP) reduced disease score, tissue damage, and inflammation and promoted the accumulation of CX3CR1+ macrophages, enhancing recovery and resolution. Here, we detail the role of immune pathology, describing a poorly characterized muscle macrophage subset as part of the dynamics of alphavirus-induced myositis and tissue recovery and identify IMP as an effective immunomodulatory approach. Given the lack of specific treatments available for alphavirus-induced pathologies, this study highlights a therapeutic potential for simple immune modulation by IMP in infected individuals in the event of large alphavirus outbreaks. IMPORTANCE Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX3CR1+ macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX3CR1+ macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.Ali ZaidKothila TharmarajahHelen MostafaviJoseph R. FreitasKuo-Ching ShengSuan-Sin FooWeiqiang ChenJelena ViderXiang LiuNicholas P. WestLara J. HerreroAdam TaylorLaura K. MackayDaniel R. GettsNicholas J. C. KingSuresh MahalingamAmerican Society for MicrobiologyarticleinflammationmacrophagesmicroparticlesmyositisRoss River virustissue repairMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammation macrophages microparticles myositis Ross River virus tissue repair Microbiology QR1-502
spellingShingle	inflammation macrophages microparticles myositis Ross River virus tissue repair Microbiology QR1-502 Ali Zaid Kothila Tharmarajah Helen Mostafavi Joseph R. Freitas Kuo-Ching Sheng Suan-Sin Foo Weiqiang Chen Jelena Vider Xiang Liu Nicholas P. West Lara J. Herrero Adam Taylor Laura K. Mackay Daniel R. Getts Nicholas J. C. King Suresh Mahalingam Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
description	ABSTRACT Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11bhi Ly6Chi inflammatory monocytes and followed by the establishment of a CD11bhi Ly6Clo CX3CR1+ macrophage population in the muscle upon recovery. Selective modulation of CD11bhi Ly6Chi monocyte migration to infected muscle using immune-modifying microparticles (IMP) reduced disease score, tissue damage, and inflammation and promoted the accumulation of CX3CR1+ macrophages, enhancing recovery and resolution. Here, we detail the role of immune pathology, describing a poorly characterized muscle macrophage subset as part of the dynamics of alphavirus-induced myositis and tissue recovery and identify IMP as an effective immunomodulatory approach. Given the lack of specific treatments available for alphavirus-induced pathologies, this study highlights a therapeutic potential for simple immune modulation by IMP in infected individuals in the event of large alphavirus outbreaks. IMPORTANCE Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX3CR1+ macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX3CR1+ macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.
format	article
author	Ali Zaid Kothila Tharmarajah Helen Mostafavi Joseph R. Freitas Kuo-Ching Sheng Suan-Sin Foo Weiqiang Chen Jelena Vider Xiang Liu Nicholas P. West Lara J. Herrero Adam Taylor Laura K. Mackay Daniel R. Getts Nicholas J. C. King Suresh Mahalingam
author_facet	Ali Zaid Kothila Tharmarajah Helen Mostafavi Joseph R. Freitas Kuo-Ching Sheng Suan-Sin Foo Weiqiang Chen Jelena Vider Xiang Liu Nicholas P. West Lara J. Herrero Adam Taylor Laura K. Mackay Daniel R. Getts Nicholas J. C. King Suresh Mahalingam
author_sort	Ali Zaid
title	Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
title_short	Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
title_full	Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
title_fullStr	Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
title_full_unstemmed	Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair
title_sort	modulation of monocyte-driven myositis in alphavirus infection reveals a role for cx<sub>3</sub>cr1<sup>+</sup> macrophages in tissue repair
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/f8569b9c0cc8402c8c2be12438a0281e
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Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX<sub>3</sub>CR1<sup>+</sup> Macrophages in Tissue Repair

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