The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

Mycobacterium tuberculosis (M. tb) causes tuberculosis infection in humans worldwide, especially among immunocompromised populations and areas of the world with insufficient funding for tuberculosis treatment. Specifically, M. tb is predominantly exhibited as a latent infection, which poses a greater risk of reactivation for infected individuals. It has been previously shown that M. tb infection requires pro-inflammatory and anti-inflammatory mediators to manage its associated granuloma formation via tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interferon-γ (IFN-γ), and caseum formation via IL-10, respectively. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) has been found to play a unique mediator role in providing a pro-inflammatory response to chronic inflammatory disease processes by promoting the activation of macrophages and the release of various cytokines such as IL-1, IL-6, IL-12, and TNF-α. NF-κB’s role is especially interesting in its mechanism of assisting the immune system’s defense against M. tb, wherein NF-κB induces IL-2 receptors (IL-2R) to decrease the immune response, but has also been shown to crucially assist in keeping a granuloma and bacterial load contained. In order to understand NF-κB’s role in reducing M. tb infection, within this literature review we will discuss the dynamic interaction between M. tb and NF-κB, with a focus on the intracellular signaling pathways and the possible side effects of NF-κB inactivation on M. tb infection. Through a thorough review of these interactions, this review aims to highlight the role of NF-κB in M. tb infection for the purpose of better understanding the complex immune response to M. tb infection and to uncover further potential therapeutic methods.

Oxidative stress is defined as the imbalance between the production of free radicals and their removal by antioxidants, leading to accumulation and subsequent organ and tissue damage. Antioxidant status and its role in the accumulation of free radicals has been observed in a number of psychological disorders. Glutathione is commonly referred to as the principal antioxidant of the brain and, therefore, plays a critical role in maintaining redox homeostasis. Reduced levels of glutathione in the brain increase its vulnerability to oxidative stress, and may be associated with the development and progression of several psychiatric disorders. Within this review, we focus on analyzing potential associations between the glutathione antioxidant pathway and psychiatric disorders: major depressive disorder, schizophrenia, bipolar disorder, and generalized anxiety disorder. Our research suggests that studies regarding these four disorders have shown decreased levels of GSH in association with diseased states; however, conflicting results note no significant variance in glutathione pathway enzymes and/or metabolites based on diseased state. In studying the potential of NAC administration as an adjunct therapy, various studies have shown NAC to augment therapy and/or aid in symptomatic management for psychiatric disorders, while contrasting results exist within the literature. Based on the conflicting findings throughout this review, there is room for study regarding the potential role of glutathione in the development and progression of psychiatric disorders. Our findings further suggest a need to study such pathways with consideration of the interactions with first-line pharmacotherapy, and the potential use of antioxidants as supplemental therapy.

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