Pathogenicity of Type I Interferons in Mycobacterium tuberculosis.

Tuberculosis (TB) is a leading cause of mortality due to infectious disease and rates have increased during the emergence of COVID-19, but many of the factors determining disease severity and progression remain unclear. Type I Interferons (IFNs) have diverse effector functions that regulate innate and adaptive immunity during infection with microorganisms. There is well-documented literature on type I IFNs providing host defense against viruses; however, in this review, we explore the growing body of work that indicates high levels of type I IFNs can have detrimental effects to a host fighting TB infection. We report findings that increased type I IFNs can affect alveolar macrophage and myeloid function, promote pathological neutrophil extracellular trap responses, inhibit production of protective prostaglandin 2, and promote cytosolic cyclic GMP synthase inflammation pathways, and discuss many other relevant findings.

Mycobacterium tuberculosis: Implications of Ageing on Infection and Maintaining Protection in the Elderly.

Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual's susceptibility to infections including Mycobacteria tuberculosis (M. tb), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of M. tb infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system. To achieve this goal, this article explores how ageing decreases the collective T-cell immune response, reduces glutathione (GSH) production, over activates the mammalian target of rapamycin (mTORC1) pathway, inhibits autophagy and mitophagy, and alters various protective genes/transcription factors. Specifically highlighting how each of these pathways cripple an individual's immune system and increases their susceptibility from M. tb infection. Furthermore, research summarized in this article gives rise to an additional mechanism of susceptibility to M. tb infection which includes a potential defect in antigen presenting by dendritic cells rather than the T-cells response. Inflammaging has also been shown to play a role in the ageing of the immune system and can also potentially be a driving factor for increased susceptibility to M. tb infection in the elderly. In addition, this article features possible preventative strategies that could decrease infections like M. tb in this population. These strategies would need to be further explored and range from immunomodulators, like Everolimus to antioxidant supplementation through GSH intake. We have also proposed the need to research these therapies in conjunction with the administration of the BCG vaccine, especially in endemic populations, to better understand the risk contracting M. tb infection as well as ways to prevent infection in the first place.