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INCREASED INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO-1) ACTIVITY AND INFLAMMATORY RESPONSES DURING CHIKUNGUNYA VIRUS INFECTION
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Abstract
Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory
responses and debilitating joint pain. Indoleamine2,3–dioxygenase 1 (IDO-1) is an enzyme that
initiates the tryptophan degradation that is important in initial host innate immune defense against
infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive
host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine
patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the
early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased
concentrations of Tumor Necrosis Factor- (TNF- ), Interleukin-6 (IL-6), Interferon
(IFN-
), C-C
motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif
chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection,
while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 (CCL4/MIP-1 )
was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis
had significantly higher concentrations of CCL4/MIP-1 compared to patients without arthritis.
Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral
effects and regulating exacerbated inflammatory responses. CCL4/MIP-1 may have an important
role in the persistent inflammation and arthritic symptoms following chikungunya infection.
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