Viruses (Nov 2020)

CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses

  • Tao Lin,
  • Tingting Geng,
  • Andrew G. Harrison,
  • Duomeng Yang,
  • Anthony T. Vella,
  • Erol Fikrig,
  • Penghua Wang

DOI
https://doi.org/10.3390/v12111252
Journal volume & issue
Vol. 12, no. 11
p. 1252

Abstract

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Emerging and re-emerging arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and O’nyong nyong virus, cause acute and chronic crippling arthralgia associated with inflammatory immune responses. Approximately 50% of CHIKV-infected patients suffer from rheumatic manifestations that last 6 months to years. However, the physiological functions of individual immune signaling pathways in the pathogenesis of alphaviral arthritis remain poorly understood. Here, we report that a deficiency in CXCL10, which is a chemoattractant for monocytes/macrophages/T cells, led to the same viremia as wild-type animals, but fewer immune infiltrates and lower viral loads in footpads at the peak of arthritic disease (6–8 days post infection). Macrophages constituted the largest immune cell population in footpads following infection, and were significantly reduced in Cxcl10−/− mice. The viral RNA loads in neutrophils and macrophages were reduced in Cxcl10−/− compared to wild-type mice. In summary, our results demonstrate that CXCL10 signaling promotes the pathogenesis of alphaviral disease and suggest that CXCL10 may be a therapeutic target for mitigating alphaviral arthritis.

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