The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced COVID-19 has emerged as a defining global health crisis in current times. Data from the World Health Organization shows demographic variations in COVID-19 severity and lethality. Diet may play a significant role in providing beneficial host cell factors contributing to immunity against deadly SARS-CoV-2 pathogenesis. Spices are essential components of the diet that possess anti-inflammatory, antioxidant, and antiviral properties. Hyperinflammation, an aberrant systemic inflammation associated with pneumonia, acute respiratory failure, and multiorgan dysfunction, is a major clinical outcome in COVID-19. Knowing the beneficial properties of spices, we hypothesize that spice-derived bioactive components can modulate host immune responses to provide protective immunity in COVID-19. This study emphasizes that biologically active components of spices might alleviate the sustained pro-inflammatory condition by inhibiting the activity of tumor necrosis factor-alpha (TNF-α), interleukins (IL6, IL8), and chemokine (CCL2) known to be elevated in COVID-19. Spices may potentially prevent the tissue damage induced by oxidative stress and pro-inflammatory mediators during SARS-CoV-2 infection. The current study also highlights the effects of spices on the antioxidant pathways mediated by Nrf2 (nuclear factor erythroid 2-related factor 2) and Hmox1 (heme oxygenase 1) to restore oxidative homeostasis and protect from aberrant tissue damage. Taken together, the anti-inflammatory and antioxidant activities of bioactive components of spices may hold a promise to target the cellular pathways for developing antivirals against SARS-CoV-2 and pan β-coronaviruses.
Meningoencephalomyelitis emanates under the umbrella relating inflammatory changes of the Central Nervous System (CNS). Meningitis denotes inflammation in the meningeal layers, encephalitis is an acute diffuse inflammation of the brain, and inflammation in the spinal cord is denoted as myelitis. These can be interrelated or independent of each other depending on the etiology. The entire mechanism of meningoencephalomyelitis is governed by an acute innate inflammatory branch followed by a chronic progressive, adaptive branch of immunity with clinical signs like hyperthermia, weight loss, hypoxia, leukocytosis. This book chapter will focus on viral-induced meningitis, encephalitis, and myelitis. Thirty years of experience working with a murine-β-coronavirus (m-CoV); Mouse hepatitis virus (MHV)-A59 induced experimental model system provided us a thorough understanding of neuroglial cell-mediated acute neuroinflammation, denoted by the accumulation of leukocyte-common-antigen (LCA) positive or CD45+ leukocytes in perivascular infiltrates referred to as perivascular cuff formation and microglial nodules in the brain parenchyma, which mimics specific pathology of human neurological disease multiple sclerosis (MS). Additionally, in this chapter, we summarized the role of CNS resident microglial activation and its interaction with peripheral migratory T cells in mounting neuropathogenesis and host immunity in different families of neurotrophic encephalomyelitis viruses that cause CNS inflammation.
Mouse hepatitis virus (MHV), a murine β‐CoV, is an experimental model used to understand the viral‐induced acute neuroinflammation and chronic progressive demyelination, which are the characteristic hallmarks of the human neurological disease Multiple Sclerosis. MHV induced neuroinflammation provides an excellent cause‐effective platform to understand how the virus can initiate neuroinflammation by causing direct neuroglial cell dystrophy, leading to chronic progressive myelin damage with or without concurrent axonal loss. Previous studies have postulated that a significant nexus between host proteins is also involved in regulating host response to viral replication. One such protein is a transmembrane protein connexin 43 (Cx43) belonging to the gap junction family. Cx43 is one of the most abundant gap junction proteins in astrocytes responsible for metabolic coupling with other CNS cells to maintain homeostasis. MHV infection in mice results in a significant decrease in the expression of Cx43 during the acute stage (day 5‐6) of MHV infection when viral titer reaches its peak and the brain presents with acute encephalitis characterized by perivascular cuffing and microglial nodule formation. Surprisingly, Cx43 returns to normal levels as infectious viral particles go below the detection limit by day 10 p.i. which marks the transition of innate immune responses to adaptive immunity. Interestingly, this reduced expression of Cx43 at Day 5 accords with increased pro‐inflammatory cytokines, oxidative stress, and activation of UPR pathway proteins. This study investigated the transcriptional regulation of TNF‐α, Il‐6, IL‐10, IL‐1β and TGF‐β in the alteration of Cx43 expression and trafficking during day 5/6 and day 10 post MHV infection. TNF‐α, IL‐10, IL‐6,IL‐1β are the major inflammatory cytokines upregulated during the acute stage of MHV infection (5‐6 p.i.). Additionally, TNF‐α and IL‐1β are known to be negative regulators of Cx43 expression and could be attributed to the decrease in Cx43 observed in our studies. Furthermore, our studies also revealed that in MHV infection, apart from the very high expression of IL‐10 another anti‐inflammatory cytokine TGF‐β expression increases when proinflammatory milieu of cytokines shifts towards the anti‐inflammatory condition in the inflamed brain. As TGF‐β is a positive regulator of Cx43, it may be responsible for the restoration of Cx43 expression and its trafficking to the cell surface resulting in functional gap junctional communication. This re‐establishment of intercellular communication maybe essential to bring back the homeostasis in the inflamed brain. The balance between pro‐inflammatory cytokines and the anti‐inflammatory mediators may regulate the host response to counteract the viral infection by altering the gap junctional communication. This study thus presents crucial evidence to support the nexus between immune inflammatory mediators and host regulatory responders in MHV induced neuroinflammation.
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