Glutathione levels and immune responses in tuberculosis patients

Venketaraman, Vishwanath; Millman, Ariel; Salman, Marwa; Swaminathan, Shobha; Goetz, M. E.; Lardizabal, Alfred; Hom, David L.; Connell, Nancy

doi:10.1016/j.micpath.2007.09.002

Cited by 82 publications

(91 citation statements)

References 19 publications

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“…Th1 immune response is known to be suppressed in patients with active TB infection (17). Interestingly, studies also indicate that patients with TB have an altered glutathione balance (18). In this context, our results demonstrate that NAC, when used at 3 mM concentration, could improve anti-BCG Th1 response in PBMC cultures obtained from patients with active TB.…”

Section: Discussionsupporting

confidence: 58%

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Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Alam

Ghousunnissa

Nair

et al. 2010

The Journal of Immunology

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Section: Discussionsupporting

confidence: 58%

“…Interestingly, studies also indicate that patients with TB have altered glutathione balance (18). However, it is not clear whether Mycobacterium tuberculosis modulates the T cell responses by altering the glutathione-redox balance in macrophages.…”

mentioning

confidence: 99%

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Alam

Ghousunnissa

Nair

et al. 2010

The Journal of Immunology

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“…Consequently, it was postulated that GSH deficiency could lead to the progression of immune dysfunction, a hallmark of TB. 16,17 In the present study levels of GSH were found to be significant decreased in serum of TB infected individuals compared to healthy controls. Various studies showed that GSH play important role in TB.…”

Section: Discussionsupporting

confidence: 52%

Assessment of oxidative stress in serum of pulmonary tuberculosis patients

et al. 2016

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“…Interestingly, studies also show that patients with AIDS or tuberculosis have an altered glutathione balance (23)(24)(25), and HIV-associated disturbances in GSH have been associated with impaired survival (26). The shift toward a Th2-dominant state and the deficiency in the induction of specific Th1 cells observed during infections may compromise the ability of the host to protect against intracellular pathogens.…”

mentioning

confidence: 99%

Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

Brundu

Palma

Picceri

et al. 2016

J Virol

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Injection of the LP-BM5 murine leukemia virus into mice causes murine AIDS, a disease characterized by many dysfunctions of immunocompetent cells. To establish whether the disease is characterized by glutathione imbalance, reduced glutathione (GSH) and cysteine were quantified in different organs. A marked redox imbalance, consisting of GSH and/or cysteine depletion, was found in the lymphoid organs, such as the spleen and lymph nodes. Moreover, a significant decrease in cysteine and GSH levels in the pancreas and brain, respectively, was measured at 5 weeks postinfection. The Th2 immune response was predominant at all times investigated, as revealed by the expression of Th1/Th2 cytokines. Furthermore, investigation of the activation status of peritoneal macrophages showed that the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arginase1, was induced. Conversely, expression of inducible nitric oxide synthase, a marker of classical activation of macrophages, was detected only when Th1 cytokines were expressed at high levels. In vitro studies revealed that during the very early phases of infection, GSH depletion and the downregulation of interleukin-12 (IL-12) p40 mRNA were correlated with the dose of LP-BM5 used to infect the macrophages. Treatment of LP-BM5-infected mice with N-(N-acetyl-L-cysteinyl)-S-acetylcysteamine (I-152),an N-acetyl-cysteine supplier, restored GSH/cysteine levels in the organs, reduced the expression of alternatively activated macrophage markers, and increased the level of gamma interferon production, while it decreased the levels of Th2 cytokines, such as IL-4 and IL-5. Our findings thus establish a link between GSH deficiency and Th1/Th2 disequilibrium in LP-BM5 infection and indicate that I-152 can be used to restore the GSH level and a balanced Th1/Th2 response in infected mice. IMPORTANCEThe first report of an association between Th2 polarization and alteration of the redox state in LP-BM5 infection is presented. Moreover, it provides evidence that LP-BM5 infection causes a decrease in the thiol content of peritoneal macrophages, which can influence IL-12 production. The restoration of GSH levels by GSH-replenishing molecules can represent a new therapeutic avenue to fight this retroviral infection, as it reestablishes the Th1/Th2 balance. Immunotherapy based on the use of pro-GSH molecules would permit LP-BM5 infection and probably all those viral infections characterized by GSH deficiency and a Th1/ Th2 imbalance to be more effectively combated. Infection with the LP-BM5 murine leukemia virus causes a profound and broad immunodeficiency in susceptible mouse strains, such as C57BL/6 (B6) mice. This disease is known as murine AIDS (MAIDS) and is characterized by early polyclonal T-and B-cell activation, splenomegaly, lymphadenopathy, hypergammaglobulinemia, decreased T-and B-cell responses, increased susceptibility to opportunistic pathogens, and the development of terminal B-cell lymphomas and neurological dysfunctions (1-4). MAIDS is charact...

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Glutathione levels and immune responses in tuberculosis patients

Cited by 82 publications

References 19 publications

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Assessment of oxidative stress in serum of pulmonary tuberculosis patients

Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

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