Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX3 CR1+ Macrophages in Tissue Repair

MBio
Ali ZaidSuresh Mahalingam

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 ...Continue Reading

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Citations

Nov 9, 2020·The Lancet Infectious Diseases·Ali ZaidSuresh Mahalingam
Jul 14, 2021·Annual Review of Virology·Vasiliya KrilAli Amara

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Methods Mentioned

BETA
PCR
flow cytometry
Confocal microscopy
fluorescence-activated cell sorting
in vitro transcription
FCS
Assay

Software Mentioned

Nanostring
Imaris
TIGR Multi Experiment Viewer
Imaris Surfaces
GraphPad Prism
nCounter
nSolver Analysis
FlowJo
Morpheus
nSolver

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