Microglia promote anti-tumour immunity and suppress breast cancer brain metastasis.

Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tumour-associated macrophages, but the role of brain-resident microglia remains controversial because they are challenging to discriminate from other tumour-associated macrophages. Using single-cell RNA sequencing, genetic and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumour-suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival and reduced natural killer and T cell responses, showing that microglia are critical to promote anti-tumour immunity to suppress BCBM. We find that the pro-inflammatory response is conserved in human microglia, and markers of their response are associated with better prognosis in patients with BCBM. These findings establish an important role for microglia in anti-tumour immunity and highlight them as a potential immunotherapy target for brain metastasis.

Potential Role of Glutathione Antioxidant Pathways in the Pathophysiology and Adjunct Treatment of Psychiatric Disorders.

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.

Role of NF-κB during Mycobacterium tuberculosis Infection.

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.

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is one of the leading causes of mortality due to respiratory tract infections worldwide. Infection by M. tb involves activation of a type I immune response characteristic of T helper type 1 (Th1) lymphocytes, natural killer (NK) cells, Interleukin-12 (IL-12), and interferon (IFN)-γ, all of which stimulate the activation of macrophages and robust phagocytosis in order to prevent further infectious manifestations and systemic dissemination. Recent discoveries about innate lymphoid cells (ILCs) have provided further insight about how these cells participate within the protective immune response against M. tb infection and help boost the type I immune response. In order to clearly understand the mechanisms of M. tb infection and advance the efficacy of future treatment and prevention, we must first look at the individual functions each type of immune cell plays within this process, specifically ILCs. By review of the recent literature and current evidence, our group aims to summarize the characterization of the three major groups of ILCs, including NK cells, and analyze the role that each group of ILCs play in the infectious process against M. tb in order to provide a more comprehensive understanding of the host immune response. Equally, previous studies have also highlighted the effects of how administration of the Bacille Calmette-Guérin (BCG) vaccine influences the cells and cytokines of the immune response against M. tb. Our group also aims to highlight the effects that BCG vaccine has on ILCs and how these effects provide added protection against M. tb.

Critical Role of Inflammation and Specialized Pro-Resolving Mediators in the Pathogenesis of Atherosclerosis.

Recent research on how the body resolves this inflammation is gaining traction and has shed light on new avenues for future management of cardiovascular diseases. In this narrative review, we discuss the pathophysiological mechanisms of atherosclerosis, the recent development in the understanding of a new class of molecules called Specialized Pro-resolving Mediators (SPMs), and the impact of such findings in the realm of cardiovascular treatment options. We searched the MEDLINE database restricting ourselves to original research articles as much as possible on the complex pathophysiology of atherosclerosis and the role of SPMs. We expect to see further research in translating these findings to bedside clinical trials in treating conditions with a pathophysiological basis of inflammation, such as coronary artery disease, asthma, and periodontal disease.

Role of Interferons in Mycobacterium tuberculosis Infection.

Considerable measures have been implemented in healthcare institutions to screen for and treat tuberculosis (TB) in developed countries; however, in low- and middle-income countries, many individuals still suffer from TB's deleterious effects. TB is caused by an infection from the Mycobacterium tuberculosis (M. tb) bacteria. Symptoms of TB may range from an asymptomatic latent-phase affecting the pulmonary tract to a devastating active and disseminated stage that can cause central nervous system demise, musculoskeletal impairments, and genitourinary compromise. Following M. tb infection, cytokines such as interferons (IFNs) are released as part of the host immune response. Three main classes of IFNs prevalent during the immune defense include: type I IFN (α and ß), type II IFN (IFN-γ), and type III IFN (IFN-λ). The current literature reports that type I IFN plays a role in diminishing the host defense against M. tb by attenuating T-cell activation. In opposition, T-cell activation drives type II IFN release, which is the primary cytokine mediating protection from M. tb by stimulating macrophages and their oxidative defense mechanisms. Type III IFN has a subsidiary part in improving the Th1 response for host cell protection against M. tb. Based on the current evidence available, our group aims to summarize the role that each IFN serves in TB within this literature review.

Protective Efficacy of BCG Vaccine against Mycobacterium leprae and Non-Tuberculous Mycobacterial Infections.

The genus mycobacterium includes several species that are known to cause infections in humans. The microorganisms are classified into tuberculous and non-tuberculous based on their morphological characteristics, defined by the dynamic relationship between the host defenses and the infectious agent. Non-tuberculous mycobacteria (NTM) include all the species of mycobacterium other than the ones that cause tuberculosis (TB). The group of NTM contains almost 200 different species and they are found in soil, water, animals-both domestic and wild-milk and food products, and from plumbed water resources such as sewers and showerhead sprays. A systematic review of Medline between 1946 and 2014 showed an 81% decline in TB incidence rates with a simultaneous 94% increase in infections caused by NTM. Prevalence of infections due to NTM has increased relative to infections caused by TB owing to the stringent prevention and control programs in Western countries such as the USA and Canada. While the spread of typical mycobacterial infections such as TB and leprosy involves human contact, NTM seem to spread easily from the environment without the risk of acquiring from a human contact except in the case of M. abscessus in patients with cystic fibrosis, where human transmission as well as transmission through fomites and aerosols has been recorded. NTM are opportunistic in their infectious processes, making immunocompromised individuals such as those with other systemic infections such as HIV, immunodeficiencies, pulmonary disease, or usage of medications such as long-term corticosteroids/TNF-α inhibitors more susceptible. This review provides insight on pathogenesis, treatment, and BCG vaccine efficacy against M. leprae and some important NTM infections.