CCR2 Deficiency Promotes Exacerbated Chronic Erosive Neutrophil-Dominated Chikungunya Virus Arthritis

• DOI: 10.1128/jvi.03364-13
• Publication Date: 2014-04-03T05:13:22Z
• Authors: Yee Suan Poo; Helder Nakaya; Joy Gardner; Thibaut Larcher; Wayne A. Schroder; Thuy T. Le; Lee D. Major; Andreas Suhrbier
• Keywords: CCR2

Chikungunya virus (CHIKV) is a member of globally distributed group arthritogenic alphaviruses that cause weeks to months debilitating polyarthritis/arthralgia, which often poorly managed with current treatments. Arthritic disease usually characterized by high levels the chemokine CCL2 and prodigious monocyte/macrophage infiltrate. Several inhibitors its receptor CCR2 are in development may find application for treatment certain inflammatory conditions, including autoimmune viral arthritides. Here we used CCR2(-/-) mice determine effect deficiency on CHIKV infection arthritis. Although there were no significant changes load or RNA persistence only marginal antiviral immunity, arthritic was substantially increased prolonged compared wild-type mice. The infiltrate replaced severe neutrophil (followed an eosinophil) associated expression multiple mediators (including CXCL1, CXCL2, granulocyte colony-stimulating factor [G-CSF], interleukin-1β [IL-1β], IL-10). loss anti-inflammatory macrophages their activities (e.g., efferocytosis) also implicated exacerbated inflammation. Clear evidence cartilage damage seen CHIKV-infected mice, feature not normally alphaviral recruitment CCR2(+) monocytes/macrophages can contribute inflammation, it appears be critical preventing excessive pathology resolving inflammation following alphavirus infection. Caution might thus warranted when considering therapeutic targeting CCR2/CCL2 arthritides.Here describe first analysis arthritis deficient CCR2. thought central monocyte/macrophage-dominated infiltrates after such as chikungunya virus. Surprisingly, caused CCR2-deficient more severe, prolonged, erosive dominated, replication being significantly affected. Monocytes/macrophages recruited appear important both even worse mediated neutrophils promoting resolution use agents target (and perhaps other viral) Individuals diminished responses (due drug reasons) at risk