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Intracellular Iron Accumulation Induces Inflammatory and Oxidative Status of the Host After Japanese Encephalitis Viral Infection

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Abstract

The factors mitigating the microglia/macrophage activation and inflammatory damage in Japanese encephalitis (JE) virus infected CNS are still being ascertained. We aim to characterize the changes in iron transporter and iron storage proteins along with inflammatory and oxidative stress-mediated signaling during the JE viral infection. Cortical tissue samples from mice with JE viral infection were processed for biochemical, histological, and molecular analysis. Iron storage protein, i.e., ferritin, was found significantly increased post-JE viral infection, and iron accumulation was noted in cortical tissue. Key proinflammatory associated markers, such as TNF-α, IL-6, and its regulator TLR4, were found to be increased, while SOCS1 (anti-inflammatory regulator) transcription decreased with increased levels of oxidative stress markers NOX2-mediated NF-ΚB/p65 and protein carbonyl. Furthermore, it is noted that hepcidin level increased and ferroportin level decreased, and iron transporter gene expression got imbalanced after JE viral infection. This observation was further confirmed by deferoxamine (DFO) treatment to JE viral infection mice model, where the decline in hepcidin transcription level and iron load in cortical tissue of JE viral infected animals was noted. However, no change was found in the ferroportin level compared to JE viral infected animals. Together, these findings suggest that iron overload and hepcidin-ferroportin regulation are involved in JE viral infection disease pathologies and associated with the inflammatory and oxidative status of the host during infection.

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Funding

The following study was supported by the Ramalingaswami Re-entry Fellowship (BT/RLF/Re-entry/13/2014) from the Department of Biotechnology, Ministry of Science and Technology, Govt. of India and Grant-in-aid Scheme of the Department of Health Research (DHR-GIA; R.11013/66/2021-GIA/HR), New Delhi to AK.

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  1. The authors Anjali Singh and Sanjay Mishra contributed equally to this paper.

Authors and Affiliations

  1. Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India

    Gajendra Singh, Anjali Singh & Alok Kumar

  2. Department of Pathology, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Sanjay Mishra & Devendra Singh

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A.K. and G.S.: writing original draft; A.K., A.S., S.M, D.D., and G.S.: methodology and data curation. All authors reviewed and edited the manuscript.

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Correspondence to Alok Kumar.

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Singh, G., Singh, A., Mishra, S. et al. Intracellular Iron Accumulation Induces Inflammatory and Oxidative Status of the Host After Japanese Encephalitis Viral Infection. Mol Neurobiol 61, 175–187 (2024). https://doi.org/10.1007/s12035-023-03538-x

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