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.