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

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-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.

• Authors: 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
• Journal: Pathogens (Basel, Switzerland) (Pathogens) Vol. 11 Issue 4 (Apr 07 2022) ISSN: 2076-0817 [Print] Switzerland
• PMID: 35456119 (Publication Type: Journal Article)