CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis

Poo, Yee Suan, Nakaya, Helder, Gardner, Joy, Larcher, Thibaut, Schroder, Wayne A., Le, Thuy T., Major, Lee D. and Suhrbier, Andreas (2014) CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis. Journal of Virology, 88 12: 6862-6872. doi:10.1128/JVI.03364-13


Author Poo, Yee Suan
Nakaya, Helder
Gardner, Joy
Larcher, Thibaut
Schroder, Wayne A.
Le, Thuy T.
Major, Lee D.
Suhrbier, Andreas
Title CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis
Journal name Journal of Virology   Check publisher's open access policy
ISSN 1098-5514
1070-6321
0022-538X
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1128/JVI.03364-13
Open Access Status DOI
Volume 88
Issue 12
Start page 6862
End page 6872
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Chikungunya virus (CHIKV) is a member of a globally distributed group of arthritogenic alphaviruses that cause weeks to months of debilitating polyarthritis/arthralgia, which is often poorly managed with current treatments. Arthritic disease is usually characterized by high levels of the chemokine CCL2 and a prodigious monocyte/macrophage infiltrate. Several inhibitors of CCL2 and its receptor CCR2 are in development and may find application for treatment of certain inflammatory conditions, including autoimmune and viral arthritides. Here we used CCR2−/− mice to determine the effect of CCR2 deficiency on CHIKV infection and arthritis. Although there were no significant changes in viral load or RNA persistence and only marginal changes in antiviral immunity, arthritic disease was substantially increased and prolonged in CCR2−/− mice compared to wild-type mice. The monocyte/macrophage infiltrate was replaced in CCR2−/− mice by a severe neutrophil (followed by an eosinophil) infiltrate and was associated with changes in the expression levels of multiple inflammatory mediators (including CXCL1, CXCL2, granulocyte colony-stimulating factor [G-CSF], interleukin-1β [IL-1β], and IL-10). The loss of anti-inflammatory macrophages and their activities (e.g., efferocytosis) was also implicated in exacerbated inflammation. Clear evidence of cartilage damage was also seen in CHIKV-infected CCR2−/− mice, a feature not normally associated with alphaviral arthritides. Although recruitment of CCR2+ monocytes/macrophages can contribute to inflammation, it also appears to be critical for preventing excessive pathology and resolving inflammation following alphavirus infection. Caution might thus be warranted when considering therapeutic targeting of CCR2/CCL2 for the treatment of alphaviral arthritides.
Keyword Chikungunya virus
Chemokine receptor Ccr2
Arthritis
Neutrophil infiltration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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