Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX(3)CR1(+) Macrophages in Tissue Repair

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Zaid, Ali
Tharmarajah, Kothila
Mostafavi, Helen
Freitas, Joseph R
Sheng, Kuo-Ching
Foo, Suan-Sin
Chen, Weiqiang
Vider, Jelena
Liu, Xiang
West, Nicholas P
Herrero, Lara J
Taylor, Adam
Mackay, Laura K
Getts, Daniel R
King, Nicholas JC
Mahalingam, Suresh
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2020
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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.

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mBio

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11

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2

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© 2020 Zaid et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Microbiology

Biochemistry and cell biology

Medical microbiology

Science & Technology

Life Sciences & Biomedicine

inflammation

macrophages

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Zaid, A; Tharmarajah, K; Mostafavi, H; Freitas, JR; Sheng, K-C; Foo, S-S; Chen, W; Vider, J; Liu, X; West, NP; Herrero, LJ; Taylor, A; Mackay, LK; Getts, DR; King, NJC; Mahalingam, S, Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX(3)CR1(+) Macrophages in Tissue Repair, mBio, 2020, 11 (2), pp. e03353-19

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