Glutathione and Adaptive Immune Responses against Mycobacterium tuberculosis Infection in Healthy and HIV Infected Individuals

Guerra, Carlos; Morris, Devin; Sipin, Andrea; Kung, Steven; Franklin, Mesharee; Gray, Dennis; Tanzil, M; Guilford, Frederick T.; Khasawneh, Fadi T.; Venketaraman, Vishwanath

doi:10.1371/journal.pone.0028378

Cited by 71 publications

(111 citation statements)

References 32 publications

(47 reference statements)

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“…Such observations are also confirmed with other antioxidants like manganese (II) mesotetrakis-(N-methylpyridinium-2-yl) porphyrin [27]. Further, glutathione is known to modulate the T cell mediated immune response in a manner that reduces the intracellular stability of the tuberculosis bacterium [28]. This fact is observed to be true for many other intracellular infection and so may be considered as a general phenomenon [29].…”

Section: Tuberculosis and The Antioxidant Paradoxsupporting

confidence: 52%

Antioxidants: Friend or foe for tuberculosis patients

Bhattacharyya¹,

Banerjee²

2013

ABB

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Respiratory burst induced bacteria killing by oxidants are important mechanism of host defence. However, it is impaired in tuberculosis due to inhibition of respiratory burst by Mycobacterial factors. Antioxidants are compounds that cause chelation of reactive oxygen species. So, antioxidants are expected to play a negative role in the management of active tuberculosis. But, oxidative stress is a proved fact that invariably happens in tuberculosis patients which is known to cause immunosuppression. Immunosuppression in turn is expected to augment tuberculosis. Hence, antioxidant supplementation is expected to benefit tuberculosis patients by minimising oxidative stress induced immunosuppression. Therefore, the role of antioxidants in tuberculosis appears to be paradoxical and urgent. Understanding of the role of antioxidant supplementation in tuberculosis is warranted. It is in this context that we have reviewed the recent literature and addressed the problem for its solution.

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Section: Tuberculosis and The Antioxidant Paradoxsupporting

confidence: 52%

Antioxidants: Friend or foe for tuberculosis patients

Bhattacharyya¹,

Banerjee²

2013

ABB

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“…However, interpretation of our results is tempered by the fact that we did not find an elevation of ROS levels in IFN-␥-primed Irgm1-deficient BMM compared with primed WT BMM. The NAC that was used in our studies is a commonly used direct ROS scavenger that also acts indirectly to quench ROS by inducing expression of glutathione (81)(82)(83). Nevertheless, some studies have found that NAC can cause effects in cells not related to ROS quenching, as a consequence of its reductive capacity and direct interaction with target proteins to modify their activities (84).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

Schmidt

Fee

Henry

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillThe immunity-related GTPases (IRGs) are a family of proteins that are induced by interferon (IFN)-␥ and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes and promote remodeling and trafficking of those membranes. Prior studies have shown that loss of Irgm1 in mice leads to increased lethality to bacterial infections as well as enhanced inflammation to non-infectious stimuli; however, the mechanisms underlying these phenotypes are unclear. In the studies reported here, we found that uninfected Irgm1-deficient mice displayed high levels of serum cytokines typifying profound autoinflammation. Similar increases in cytokine production were also seen in cultured, IFN-␥-primed macrophages that lacked Irgm1. A series of metabolic studies indicated that the enhanced cytokine production was associated with marked metabolic changes in the Irgm1-deficient macrophages, including increased glycolysis and an accumulation of long chain acylcarnitines. Cells were exposed to the glycolytic inhibitor, 2-deoxyglucose, or fatty acid synthase inhibitors to perturb the metabolic alterations, which resulted in dampening of the excessive cytokine production. These results suggest that Irgm1 deficiency drives metabolic dysfunction in macrophages in a manner that is cell-autonomous and independent of infectious triggers. This may be a significant contributor to excessive inflammation seen in Irgm1-deficient mice in different contexts.

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“…TNF-α is elevated during HIV progression and is negatively correlated with GSH and also serves as a second messenger in oxidative stress [25, 60]. Also, studies have demonstrated that depleted GSH in HIV positive individuals [61] play a major role in the apoptosis of CD4 + T cells [62]. Furthermore, GSH levels in DC which maintains redox homeostasis and protecting DCs from oxidative stress are highly specialized in their ability to process and present exogenous antigen to CD4+ T helper cells and endogenous antigen to CD8+ T cells and accordingly influence the immune response by Th1 cytokine secretion [63–65].…”

Section: Discussionmentioning

confidence: 99%

Immunoneuropathogenesis of HIV-1 clades B and C: Role of redox expression and thiol modification

Samikkannu

Rao

Kanthikeel

et al. 2014

Free Radical Biology and Medicine

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Previous studies have shown that infection with HIV-1 clade B and clade C differentially contributes to the neuropathogenesis and development of HIV-associated neurocognitive disorders (HAND). The low molecular weight tripeptide glutathione (GSH) alters the redox balance and leads to the generation of reactive oxygen species (ROS), which play a significant role in the neuropathogenesis of HAND. We hypothesized that the HIV-1 clade B and clade C viruses and the respective Tat proteins exert differential effects on monocyte (MC)-derived immature dendritic cells (IDC) and neuroblastoma cells (SK-N-MC) by redox activation, which leads to immuno-neuropathogenesis. The GSH/GSSG ratio and mRNA expression levels and protein modification of glutathione synthetase (GSS), glutathione peroxidase 1 (GPx1), superoxide dismutase 1 (SOD1) and catalase (CAT) were analyzed in IDC infected with HIV-1 clade B or clade C as well as in cells treated with the respective Tat proteins. The results indicated that HIV-1 clade B virus and its Tat protein significantly increased the production of reactive oxygen species (ROS) and reduced the GSH/GSSG ratio and subsequent down-regulation of gene expression and protein modification of GSS, GPx1, SOD1 and CAT than infection with the clade C virus or treatment with the clade C Tat protein. Thus, our studies demonstrate that HIV-1 clade B and C exert differential effects of redox expression and thiol modification. HIV-1 clade B potentially induces oxidative stress, leading to more immuno-neuropathogenesis than infection with HIV-1 clade C.

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Glutathione and Adaptive Immune Responses against Mycobacterium tuberculosis Infection in Healthy and HIV Infected Individuals

Cited by 71 publications

References 32 publications

Antioxidants: Friend or foe for tuberculosis patients

Antioxidants: Friend or foe for tuberculosis patients

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

Immunoneuropathogenesis of HIV-1 clades B and C: Role of redox expression and thiol modification

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