Key result
Minocycline and PP2 show promising anti-inflammatory and anti-viral activity in monocytic cell-driven Japanese encephalitis.
Understanding the cellular and molecular mechanisms of JEV-induced neuroinflammation is critical for developing specific curative treatments that avoid detrimental inflammatory responses.
Monocytic cells may drive JE neuroinflammation; hypothesis-generating for targeted immunomodulation pending interventional trials.
BACKGROUND: Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis. MAIN BODY: Brain-infiltrating monocytes, macrophages and microglia play a major role in central nervous system (CNS) inflammation during JE. Moreover, the role of inflammatory monocytes in viral neuroinvasion during JE and mechanisms of cell entry into the CNS remains unclear. The identification of cellular and molecular actors in JE inflammatory responses may help to understand the mechanisms behind excessive inflammation and to develop therapeutics to treat JE patients. This review addresses the current knowledge about mechanisms of virus neuroinvasion, neuroinflammation and therapeutics critical for JE outcome. CONCLUSION: Understanding the regulation of inflammation in JE is challenging. Elucidation of the remaining open questions will help to the development of therapeutic approaches avoiding detrimental inflammatory responses in JE.
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Lannes et al. (2017) conducted a review in Japanese encephalitis. Cells of the monocytic lineage play a central role in inflammatory responses and pathogenesis in Japanese encephalitis, while therapeutic candidates like minocycline and PP2 present promising anti-inflammatory and anti-viral activity.
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