The Interplay Between Systemic Inflammation, Oxidative Stress, and Tissue Remodeling in Tuberculosis

Abstract

Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is also triggered in chronically inflamed sites, facilitating a wide spectrum of clinical manifestations. Recent Advances: Since persistent and exacerbated oxidative stress responses have been associated with severe pathology, a number of studies have suggested that the inhibition of this augmented stress response by improving host antioxidant status may represent a reasonable strategy to ameliorate tissue damage in TB. Critical Issues: This review summarizes the interplay between oxidative stress, systemic inflammation and tissue remodeling, and its consequences in promoting TB disease. We emphasize the most important mechanisms associated with stress responses that contribute to the progression of TB. We also point out important host immune components that may influence the exacerbation of cellular stress and the subsequent tissue injury. Future Directions: Further research should reveal valuable targets for host-directed therapy of TB, preventing development of severe immunopathology and disease progression. Antioxid. Redox Signal. 00, 000-000.

Variations of Serum Oxidative Stress Biomarkers under First-Line Antituberculosis Treatment: A Pilot Study

“…Enzymatic antioxidants are present in higher concentrations in erythrocytes, and were thus quantified using hemolysates. Cellular oxidative damage, loss of mitochondrial membrane integrity, and impaired cellular function can also be controlled through glutathione activity, which regulates the redox cycle and maintains antioxidant functionality of ascorbic acid and tocopherol [8,[14][15][16]. After 60 days of first-line treatment, GSH values increased, with its possible involvement in modulating cytokine activity and host response [17].…”

“…membrane disruption by affecting the double chemical bonds of polyunsaturated lipids [5]. Even more highly toxic and powerful free radicals, such as superoxide (O 2 -) and hydroxyl (OH -), are generated after mitochondrial oxidative burst [16]. However, M.tb.…”

Persistent oxidative stress and inflammasome activation in CD14highCD16-monocytes from COVID-19 patients

“…Several stress-related cellular processes have been reported to induce NLRP3 activation in response to distinct PAMPs and DAMPs, such as K + efflux (Munoz-Planillo et al, 2013), lysosomal disruption (Hornung et al, 2008), mitochondrial damage (Iyer et al, 2013; Zhou et al, 2011) and the generation of reactive oxygen species (ROS) (Martinon, 2010; Tschopp and Schroder, 2010). Since robust redox responses observed in hypoxic conditions during other pulmonary infections are commonly associated with exacerbated cytokine production and disease progression (Amaral et al, 2021; Erlich et al, 2020; Favier et al, 1994; Freeborn and Rockwell, 2021; Pohanka, 2013; Prabhakar et al, 2020), host oxidative stress has also been implicated in the pathogenesis of COVID-19 (Delgado-Roche and Mesta, 2020; Fakhri et al, 2020; Ntyonga-Pono, 2020).…”

Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV

“…On the molecular level, full myeloid activation resulting from CD4 + T-cell IFN signal leads to a cytokine storm orchestrated by monocyte and macrophage populations with a higher production of matrix metalloproteinases (MMPs) [ 77 , 78 ]. The imbalance between MMP levels and tissue inhibitors of metalloproteinase (TIMPs) outpaces collagen deposition leading to tissue remodeling [ 78 ]. Importantly, MMP/TIMP dysregulated production was associated with cavitation and, consequently, bacterial proliferation [ 79 ], which could cause suppurative manifestations.…”