Pathogens (Apr 2022)

Increased Indoleamine 2,3-Dioxygenase 1 (IDO-1) Activity and Inflammatory Responses during Chikungunya Virus Infection

  • Thiara Manuele Alves de Souza,
  • Caroline Fernandes-Santos,
  • Jéssica Araújo da Paixão de Oliveira,
  • Larissa Cristina Teixeira Tomé,
  • Victor Edgar Fiestas-Solórzano,
  • Priscila Conrado Guerra Nunes,
  • Gabriel Macedo Costa Guimaraes,
  • Juan Camilo Sánchez-Arcila,
  • Iury Amâncio Paiva,
  • Luís Jose de Souza,
  • Paulo Vieira Damasco,
  • Válber da Silva Frutuoso,
  • Manoela Heringer,
  • Luzia Maria de Oliveira-Pinto,
  • Roberta Olmo Pinheiro,
  • Flavia Barreto dos Santos,
  • Elzinandes Leal de Azeredo

DOI
https://doi.org/10.3390/pathogens11040444
Journal volume & issue
Vol. 11, no. 4
p. 444

Abstract

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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-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), 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 β (CCL4/MIP-1β) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1β 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-1β may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection.

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