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Innate immune response in patients with acute Chikungunya disease

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Abstract

Chikungunya disease (CHIKD) is an arbovirose that presents with high morbidity, mainly due to arthralgia. Inflammatory mediators including IL-6, IL-1β, GM-CSF and others have been implicated in the pathogenesis of CHIKD, whilst type I interferons can be associated with better outcomes. The role of pattern recognition receptors has been studied incompletely. Here, we evaluated the expression of RNA-specific PRRs, their adaptor molecules and downstream cytokines in acute CHIKD patients. Twenty-eight patients were recruited during the 3rd–5th day after the symptoms onset for clinical examination, peripheral blood collection and qRT-PCR analysis of PBMC to compare to the healthy control group (n = 20). We observed common symptoms of acute CHIKD, with fever, arthralgia, headache and myalgia being the most frequent. Compared with uninfected controls, acute CHIKV infection upregulates the expression of the receptors TLR3, RIG-I and MDA5, and also the adaptor molecule TRIF. Regarding cytokine expression, we found an upregulation of IL-6, IL-12, IFN-α, IFN-β and IFN-γ, which are related directly to the inflammatory or antiviral response. The TLR3-TRIF axis correlated with high expression of IL-6 and IFN-α. Interestingly, greater expression of MDA5, IL-12 and IFN-α was related to lower viral loads in CHIKD acute patients. Together, these findings help to complete the picture of innate immune activation during acute CHIKD, while confirming the induction of strong antiviral responses. Drawing the next steps in the understanding of the immunopathology and virus clearance mechanisms of CHIKD should be of utter importance in the aid of the development of effective treatment to reduce the severity of this debilitating disease.

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Acknowledgements

The authors thank the financial support by the National Council for Scientific and Technological Development (CNPq Grants no. 400328/2014-3, 404904/2016-5 and 311055/2019-2) and the Brazilian Federal.

Funding

This work was supported by the National Council for Scientific and Technological Development—CNPq [Grants n.º 311055/2019-2; n.º 404904/2016-5; 400328/2014-3] and the Brazilian Federal Agency for Support and Evaluation of Graduate Education—CAPES. Agency for Support and Evaluation of Graduate Education—CAPES.

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  1. Wallace Pitanga Bezerra, Raíza Nara Cunha Moizéis and Amanda Costa Ayres Salmeron are co-first authors.

  2. José Veríssimo Fernandes and Manuela Sales Lima Nascimento are co-last authors.

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  1. Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte. Natal, Rio Grande do Norte, Natal, Rio Grande Do Norte, 59078-970, Brazil

    Wallace Pitanga Bezerra, Raíza Nara Cunha Moizéis, Hannaly Wana Bezerra Pereira, Josélio Maria Galvão de Araújo, Paulo Marcos Matta Guedes, José Veríssimo Fernandes & Manuela Sales Lima Nascimento

  2. Edmond and Lily Safra International Institute of Neuroscience, Santos Dumont Institute, Macaiba, Rio Grande do Norte, Brazil

    Amanda Costa Ayres Salmeron & Manuela Sales Lima Nascimento

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WPB: conceptualization, formal analysis, investigation, roles/writing—original draft and writing—review & editing; RNCM: conceptualization, methodology and investigation; ACAS: conceptualization, formal analysis, investigation, roles/writing—original draft and writing—review & editing; HWBP: methodology and investigation; JMGdA: methodology, investigation, funding acquisition and writing—review & editing; PMdMG: methodology, formal analysis, investigation, funding acquisition and writing—review & editing; José VF: conceptualization, formal analysis, investigation, funding acquisition, writing—review & editing and supervision; MSLN: conceptualization, formal analysis, investigation, funding acquisition, roles/writing—original draft; writing—review & editing and supervision.

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Correspondence to Manuela Sales Lima Nascimento.

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The study was approved by the Research Ethics Committee, with a Certificate from the Brazilian System of Ethics in Research (CAEE-SISNEP) protocol number CAAE: 51057015.5.0000.5537. All procedures performed in this study involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments.

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Bezerra, W.P., Moizéis, R.N.C., Salmeron, A.C.A. et al. Innate immune response in patients with acute Chikungunya disease. Med Microbiol Immunol 212, 279–290 (2023). https://doi.org/10.1007/s00430-023-00771-y

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