Increased Indoleamine 2,3-Dioxygenase 1 (IDO-1) Activity and Inflammatory Responses during Chikungunya Virus Infection
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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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Other neurotropic viruses, including chikungunya virus, activate the kynurenine pathway through exerting antiviral effects and exacerbating inflammatory responses.
“other neurotropic viruses, including chikungunya virus (CHIKV), activate the KP, through exerting antiviral effects and exacerbating inflammatory responses [42].”
From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [42]
The Discussion reports increased IDO-1 activity during early CHIKV infection and suggests it could have an antiviral effect. But it says IDO-1 may protect against uncontrolled immune responses and attenuate inflammation—not exacerbate it. The paper also does not establish this finding for other neurotropic viruses. (LLM, conf=0.87)
Experimental — accuracy not yet measuredClinical studies identified heightened IDO activity, increased KYN/TRP ratios, and increased concentrations of TNF-α, IL-6, IFN-γ, CCL2, and CXCL10 in CHIKV patients.
“This is further supported by clinical studies identifying heightened IDO activity, increased KYN/TRP ratios, and increase concentrations of TNF-α, IL-6, IFN-γ, CCL2, and CXCL10 in CHIKV patients [42].”
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Innate immune sensing of alphavirus chikungunya: balancing antiviral defense and pathogenesis
da Silva, J. S. D. F., Ferreira, C. V., dos Santos, L. M. S., de Andrade‐Neto, V. F., Guedes, P. M. D. M., Yaochite, J. N. U., França, R. F. D. O., Brito, R. M. D. M., & Nascimento, M. S. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1810208 · Cited by 3 · see citing works
“However, another study also found the production of IL-8/CXCL8, CCL2/MCP-1, IL-6, MIP-1 a , and MIP-1 b to be increased during chronic phase (171), while CCL5 was decreased during acute phase (174).”
Fernandes-Santos, C., Nunes, P. C. G., Solórzano, V. F., Gandini, M., dos Santos, F. B., Pinheiro, R. O., de Souza, L. J., Damasco, P. V., Pinto, L. M. D. O., & de Azeredo, E. L. (2025) · Viruses · doi:10.3390/v17091224 · Cited by 6 · see citing works
“The pathogenesis of infection is also associated with elevated levels of inflammatory mediators, such as cytokines and chemokines [2,7].”
Self-citationJose, S., Jerome, R., Krishnan, A., Jagan, O., Li, D.-M., & Menon, V. P. (2023) · Viral immunology · doi:10.1089/vim.2022.0160 · Cited by 1 · see citing works
- Authors
- Alves de Souza, T., Fernandes-Santos, C., Araújo da Paixão de Oliveira, J., Tomé, L., Fiestas-Solórzano, V., Nunes, P., Guimaraes, G., Sánchez-Arcila, J., Paiva, I., de Souza, L., Damasco, P., da Silva Frutuoso, V., Heringer, M., de Oliveira-Pinto, L., Pinheiro, R., dos Santos, F., & Leal de Azeredo, E.
- Affiliations
- Viral Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, Brazil
- Instituto Oswaldo Cruz (BR)
- Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, Brazil
- Reference Center for Immune and Infectious Diseases (CRDI), Faculty of Medicine, Campos dos Goytacazes, Brazil Campos dos Goytacazes, Rio de Janeiro 28025-496, Brazil
- Hospital Universitário Gaffrée e Guinle (BR)
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, Brazil
- Instituto Estadual do Cérebro Paulo Niemeyer (BR)
- ORCID
- Venue
- Pathogens
- Publisher
- MDPI AG
- Published
- 2022-04-07
- Volume
- 11
- Issue
- 4
- Pages
- 444
- ISSN
- 2076-0817 (ISSN-L)
- PMC
- PMC9028473
- OpenAlex
- W4224262261
- Cited by
- 15
- References
- 69
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 3
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (E-26/210.268/2019, E-26/010.002420/2019, 26/201/244/2021)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- chikungunya virus, IDO1, tryptophan metabolism, kynurenine/tryptophan ratio, inflammatory cytokines, chemokines, arthritis, chronic inflammation, acute phase of infection, TNF-α, interleukin-6, interferon-gamma, antiviral immunity
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