Redox regulation of immunity

This data summary table collects studies showing how redox and Nrf2 regulate immunity and infections. I may finish a full post on this at some point.

References

1.           Liang, J. et al. Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione. Front. Immunol. 9, 2584 (2018).

2.           Zagorski, J. W. et al. Differential effects of the Nrf2 activators tBHQ and CDDO-Im on the early events of T cell activation. Biochem. Pharmacol. 147, 67–76 (2018).

3.           Wen, Z. et al. A Protective Role of the NRF2-Keap1 Pathway in Maintaining Intestinal Barrier Function. Oxid. Med. Cell. Longev. 2019, 1759149 (2019).

4.           Zhao, R. et al. Nasal epithelial barrier disruption by particulate matter ≤2.5 μm via tight junction protein degradation. J. Appl. Toxicol. 38, 678–687 (2018).

5.           Kouadri, A. et al. Involvement of the Prion Protein in the Protection of the Human Bronchial Epithelial Barrier Against Oxidative Stress. Antioxid. Redox Signal. 31, 59–74 (2019).

6.           Haddad, J. J. A redox microenvironment is essential for MAPK-dependent secretion of pro-inflammatory cytokines: modulation by glutathione (GSH/GSSG) biosynthesis and equilibrium in the alveolar epithelium. Cell. Immunol. 270, 53–61 (2011).

7.           Øvrevik, J., Refsnes, M., Låg, M., Holme, J. A. & Schwarze, P. E. Activation of proinflammatory responses in cells of the airway mucosa by particulate matter: Oxidant- and non-oxidant-mediated triggering mechanisms. Biomolecules 5, 1399–1440 (2015).

8.           Khomich, O. A., Kochetkov, S. N., Bartosch, B. & Ivanov, A. V. Redox biology of respiratory viral infections. Viruses 10, (2018).

9.           Manzel, L. J., Shi, L., O’Shaughnessy, P. T., Thorne, P. S. & Look, D. C. Inhibition by cigarette smoke of nuclear factor-κB-dependent response to bacteria in the airway. Am. J. Respir. Cell Mol. Biol. 44, 155–65 (2011).

10.        Modestou, M. A., Manzel, L. J., El-Mahdy, S. & Look, D. C. Inhibition of IFN-gamma-dependent antiviral airway epithelial defense by cigarette smoke. Respir. Res. 11, 64 (2010).

11.        Bauer, C. M. T. et al. Cigarette smoke suppresses type I interferon-mediated antiviral immunity in lung fibroblast and epithelial cells. J. Interferon Cytokine Res. 28, 167–79 (2008).

12.        Menzel, M. et al. Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients. Front. Immunol. 10, 2765 (2019).

13.        Chen, X. et al. Urban particulate matter (PM) suppresses airway antibacterial defence. Respir. Res. 19, 5 (2018).

14.        Singh, R. et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat. Commun. 10, 89 (2019).

15.        London, N. R. et al. Nrf2 activation via Keap1 deletion or sulforaphane treatment reduces Ova‐induced sinonasal inflammation. Allergy 74, 1780–1783 (2019).

16.        Sussan, T. E. et al. Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function. Am. J. Physiol. Lung Cell. Mol. Physiol. 309, L27-36 (2015).

17.        Kesic, M. J., Simmons, S. O., Bauer, R. & Jaspers, I. Nrf2 expression modifies influenza A entry and replication in nasal epithelial cells. Free Radic. Biol. Med. 51, 444–53 (2011).

18.        Dai, J. et al. Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways. Int. Immunopharmacol. 54, 177–187 (2018).

19.        Meyer, M. et al. Sulforaphane induces SLPI secretion in the nasal mucosa. Respir. Med. 107, 472–5 (2013).

20.        Mihaylova, V. T. et al. Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. Cell Rep. 24, 3000-3007.e3 (2018).

21.        Olagnier, D. et al. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming. Nat. Commun. 9, 3506 (2018).

22.        Cieslik, K. A. et al. Improved Cardiovascular Function in Old Mice After N-Acetyl Cysteine and Glycine Supplemented Diet: Inflammation and Mitochondrial Factors. J. Gerontol. A. Biol. Sci. Med. Sci. 73, 1167–1177 (2018).

23.        Sekhar, R. V, Liu, C. W. & Rice, S. Increasing glutathione concentrations with cysteine and glycine supplementation lowers inflammation in HIV patients. AIDS 29, 1899–900 (2015).

24.        Arnalich, F. et al. Intracellular glutathione deficiency is associated with enhanced nuclear factor-kappaB activation in older non-insulin dependent diabetic patients. Free Radic. Res. 35, 873–84 (2001).

25.        Cordero, M. D. et al. NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10. Antioxid. Redox Signal. 20, 1169–80 (2014).

26.        Kim, V. Y. et al. Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic Candida albicans Infection in Mice. J. Immunol. 203, 2239–2251 (2019).

27.        Reddy, N. M. et al. Innate immunity against bacterial infection following hyperoxia exposure is impaired in NRF2-deficient mice. J. Immunol. 183, 4601–8 (2009).

28.        Limongi, D. et al. GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition. Front. Immunol. 10, 155 (2019).

29.        Thimmulappa, R. K. et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 116, 984–95 (2006).

30.        Lavieri, R., Rubartelli, A. & Carta, S. Redox stress unbalances the inflammatory cytokine network: role in autoinflammatory patients and healthy subjects. J. Leukoc. Biol. 99, 79–86 (2016).

31.        Yan, J. et al. Glutathione reductase facilitates host defense by sustaining phagocytic oxidative burst and promoting the development of neutrophil extracellular traps. J. Immunol. 188, 2316–27 (2012).

32.        Yan, J. et al. Glutathione reductase is essential for host defense against bacterial infection. Free Radic. Biol. Med. 61C, 320–332 (2013).

33.        Villa, P., Saccani, A., Sica, A. & Ghezzi, P. Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense. J. Infect. Dis. 185, 1115–20 (2002).

34.        Chatterjee, M. et al. Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst. Free Radic. Biol. Med. 45, 1084–93 (2008).

35.        Bozonet, S. M., Carr, A. C., Pullar, J. M. & Vissers, M. C. M. Enhanced human neutrophil vitamin C status, chemotaxis and oxidant generation following dietary supplementation with vitamin C-rich SunGold kiwifruit. Nutrients 7, 2574–88 (2015).

36.        Garg, S., Vitvitsky, V., Gendelman, H. E. & Banerjee, R. Monocyte differentiation, activation, and mycobacterial killing are linked to transsulfuration-dependent redox metabolism. J. Biol. Chem. 281, 38712–20 (2006).

37.        Viora, M. et al. Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine. Immunology 104, 431–8 (2001).

38.        Malorni, W. et al. Oxidized low-density lipoproteins affect natural killer cell activity by impairing cytoskeleton function and altering the cytokine network. Exp. Cell Res. 236, 436–45 (1997).

39.        Tsuyuki, S. et al. N-acetylcysteine improves cytotoxic activity of cirrhotic rat liver-associated mononuclear cells. Int. Immunol. 10, 1501–8 (1998).

40.        Hanson, M. G. V et al. A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients. Cancer Immunol. Immunother. 56, 973–84 (2007).

41.        Vojdani, A. et al. Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15. J. Neuroimmunol. 205, 148–54 (2008).

42.        Chernyshov, V. P. et al. Up-regulation of interferon-gamma production by reduced glutathione, anthocyane and L-cysteine treatment in children with allergic asthma and recurrent respiratory diseases. Russ. J. Immunol. 7, 48–56 (2002).

43.        Richie, J. P. et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur. J. Nutr. 54, 251–63 (2015).

44.        Sinha, R. et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur. J. Clin. Nutr. 72, 105–111 (2018).

45.        Kuppner, M. C. et al. Differential effects of ifosfamide on dendritic cell-mediated stimulation of T cell interleukin-2 production, natural killer cell cytotoxicity and interferon-gamma production. Clin. Exp. Immunol. 153, 429–38 (2008).

46.        Zhang, G., Nichols, R. D., Taniguchi, M., Nakayama, T. & Parmely, M. J. Gamma interferon production by hepatic NK T cells during Escherichia coli infection is resistant to the inhibitory effects of oxidative stress. Infect. Immun. 71, 2468–77 (2003).

47.        Kosmider, B. et al. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir. Res. 13, 43 (2012).

48.        Loboda, A. et al. HIF-1 induction attenuates Nrf2-dependent IL-8 expression in human endothelial cells. Antioxid. Redox Signal. 11, 1501–17 (2009).

49.        Zhang, X., Chen, X., Song, H., Chen, H.-Z. & Rovin, B. H. Activation of the Nrf2/antioxidant response pathway increases IL-8 expression. Eur. J. Immunol. 35, 3258–67 (2005).

50.        Seelige, R. et al. Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection. Sci. Rep. 8, 13670 (2018).

51.        Kobayashi, E. H. et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun. 7, 11624 (2016).

52.        Mills, E. L. et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556, 113–117 (2018).

53.        Piantadosi, C. A. et al. Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. J. Biol. Chem. 286, 16374–85 (2011).

54.        Hennig, P. et al. The Crosstalk between Nrf2 and Inflammasomes. Int. J. Mol. Sci. 19, 562 (2018).

55.        Nadeem, A. et al. Differential regulation of Nrf2 is linked to elevated inflammation and nitrative stress in monocytes of children with autism. Psychoneuroendocrinology 113, 104554 (2020).

56.        Wu, M. et al. Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia. Am. J. Physiol. Lung Cell. Mol. Physiol. 313, L138–L153 (2017).

57.        Reddy, N. M., Potteti, H. R., Mariani, T. J., Biswal, S. & Reddy, S. P. Conditional deletion of Nrf2 in airway epithelium exacerbates acute lung injury and impairs the resolution of inflammation. Am. J. Respir. Cell Mol. Biol. 45, 1161–8 (2011).

58.        Olagnier, D. et al. Nrf2, a PPARγ alternative pathway to promote CD36 expression on inflammatory macrophages: implication for malaria. PLoS Pathog. 7, e1002254 (2011).

59.        Staitieh, B. S. et al. HIV-1 decreases Nrf2/ARE activity and phagocytic function in alveolar macrophages. J. Leukoc. Biol. 102, 517–525 (2017).

60.        Kong, X. et al. Enhancing Nrf2 pathway by disruption of Keap1 in myeloid leukocytes protects against sepsis. Am. J. Respir. Crit. Care Med. 184, 928–38 (2011).

61.        Bewley, M. A. et al. Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. Am. J. Respir. Crit. Care Med. 198, 739–750 (2018).

62.        Harvey, C. J. et al. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci. Transl. Med. 3, 78ra32 (2011).

63.        Kadl, A. et al. Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2. Circ. Res. 107, 737–46 (2010).

64.        Helou, D. G. et al. Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration. PLoS One 14, e0216465 (2019).

65.        Kumar, P. et al. IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Sci. Rep. 9, 4984 (2019).

66.        Boss, A. P. et al. The Nrf2 activator tBHQ inhibits the activation of primary murine natural killer cells. Food Chem. Toxicol. 121, 231–236 (2018).

67.        Rojo, A. I. et al. Redox control of microglial function: molecular mechanisms and functional significance. Antioxid. Redox Signal. 21, 1766–801 (2014).

68.        Garg, G., Singh, S., Singh, A. K. & Rizvi, S. I. N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging. Can. J. Physiol. Pharmacol. 96, 1189–1196 (2018).

69.        Cruz, J. C., Flôr, A. F. L., França-Silva, M. S., Balarini, C. M. & Braga, V. A. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome. Front. Physiol. 6, 384 (2015).

70.        Chan, S. H. H. & Chan, J. Y. H. Brain stem oxidative stress and its associated signaling in the regulation of sympathetic vasomotor tone. J. Appl. Physiol. 113, 1921–8 (2012).

71.        Rao, X., Zhong, J., Brook, R. D. & Rajagopalan, S. Effect of Particulate Matter Air Pollution on Cardiovascular Oxidative Stress Pathways. Antioxidants Redox Signal. 28, 797–818 (2018).

72.        Liu, C. et al. Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes. Part. Fibre Toxicol. 11, 53 (2014).

73.        Alfieri, A. et al. Sulforaphane preconditioning of the Nrf2/HO-1 defense pathway protects the cerebral vasculature against blood-brain barrier disruption and neurological deficits in stroke. Free Radic. Biol. Med. 65, 1012–1022 (2013).

74.        Zhao, X. et al. Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance. J. Neurochem. 133, 144–52 (2015).

75.        Trujillo, J. a et al. The cellular redox environment alters antigen presentation. J. Biol. Chem. 289, 27979–91 (2014).

76.        Weiskopf, D. et al. Oxidative stress can alter the antigenicity of immunodominant peptides. J. Leukoc. Biol. 87, 165–72 (2010).

77.        Griffiths, H. R., Rooney, M. C. O. & Perrie, Y. Does Dysregulation of Redox State Underpin the Decline of Innate Immunity with Aging? Antioxid. Redox Signal. 32, 1014–1030 (2020).

78.        Carilho Torrao, R. B. D., Dias, I. H., Bennett, S. J., Dunston, C. R. & Griffiths, H. R. Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion. Chem. Cent. J. 7, 150 (2013).

79.        Kesarwani, P., Murali, A. K., Al-Khami, A. A. & Mehrotra, S. Redox regulation of T-cell function: from molecular mechanisms to significance in human health and disease. Antioxid. Redox Signal. 18, 1497–534 (2013).

80.        Mensurado, S. et al. Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress. PLoS Biol. 16, e2004990 (2018).

81.        Bouamama, S., Merzouk, H., Medjdoub, A., Merzouk-Saidi, A. & Merzouk, S. A. Effects of exogenous vitamins A, C, and E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects. Appl. Physiol. Nutr. Metab. 42, 579–587 (2017).

82.        Marthandan, S., Hyland, P., Pawelec, G. & Barnett, Y. An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells. Immun. Ageing 10, 7 (2013).

83.        Jariwalla, R. J. et al. Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection. J. Altern. Complement. Med. 14, 139–46 (2008).

84.        Seyerl, M. et al. Oxidized phospholipids induce anergy in human peripheral blood T cells. Eur. J. Immunol. 38, 778–87 (2008).

85.        Sha, L. K. et al. Loss of Nrf2 in bone marrow-derived macrophages impairs antigen-driven CD8(+) T cell function by limiting GSH and Cys availability. Free Radic. Biol. Med. 83, 77–88 (2015).

86.        Mougiakakos, D., Johansson, C. C., Jitschin, R., Böttcher, M. & Kiessling, R. Increased thioredoxin-1 production in human naturally occurring regulatory T cells confers enhanced tolerance to oxidative stress. Blood 117, 857–61 (2011).

87.        Mak, T. W. et al. Glutathione Primes T Cell Metabolism for Inflammation. Immunity 46, 675–689 (2017).

88.        Li, N. & Buglak, N. Convergence of air pollutant-induced redox-sensitive signals in the dendritic cells contributes to asthma pathogenesis. Toxicol. Lett. 237, 55–60 (2015).

89.        Agrawal, A., Kaushal, P., Agrawal, S., Gollapudi, S. & Gupta, S. Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells. J. Leukoc. Biol. 81, 474–82 (2007).

90.        Kim, H.-J., Barajas, B., Wang, M. & Nel, A. E. Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells. J. Allergy Clin. Immunol. 121, 1255-1261.e7 (2008).

91.        Peterson, J. D., Herzenberg, L. a, Vasquez, K. & Waltenbaugh, C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc. Natl. Acad. Sci. U. S. A. 95, 3071–6 (1998).

92.        Aizawa, H. et al. Oxidative stress enhances the expression of IL-33 in human airway epithelial cells. Respir. Res. 19, 52 (2018).

93.        Frossi, B., De Carli, M., Piemonte, M. & Pucillo, C. Oxidative microenvironment exerts an opposite regulatory effect on cytokine production by Th1 and Th2 cells. Mol. Immunol. 45, 58–64 (2008).

94.        Murata, Y., Shimamura, T. & Hamuro, J. The polarization of T(h)1/T(h)2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production. Int. Immunol. 14, 201–12 (2002).

95.        Ly, J. et al. Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals. J. Interferon Cytokine Res. 35, 875–87 (2015).

96.        Malmberg, K.-J. et al. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin. Cancer Res. 8, 1772–8 (2002).

97.        Al-Huseini, L. M. A. et al. Heme oxygenase-1 regulates dendritic cell function through modulation of p38 MAPK-CREB/ATF1 signaling. J. Biol. Chem. 289, 16442–51 (2014).

98.        Moon, S.-J. et al. Rebamipide suppresses collagen-induced arthritis through reciprocal regulation of th17/treg cell differentiation and heme oxygenase 1 induction. Arthritis Rheumatol. (Hoboken, N.J.) 66, 874–85 (2014).

99.        Hammer, A. et al. Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells. Front. Immunol. 8, 1922 (2017).

100.      Noel, S. et al. T Lymphocyte-Specific Activation of Nrf2 Protects from AKI. J. Am. Soc. Nephrol. 26, 2989–3000 (2015).

101.      Klemm, P. et al. Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice. Eur. J. Immunol. 50, 515–524 (2020).

102.      Li, N. et al. Nrf2 deficiency in dendritic cells enhances the adjuvant effect of ambient ultrafine particles on allergic sensitization. J. Innate Immun. 5, 543–54 (2013).

103.      Rockwell, C. E., Zhang, M., Fields, P. E. & Klaassen, C. D. Th2 skewing by activation of Nrf2 in CD4(+) T cells. J. Immunol. 188, 1630–7 (2012).

104.      Sireesh, D., Dhamodharan, U., Ezhilarasi, K., Vijay, V. & Ramkumar, K. M. Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus. Sci. Rep. 8, 5126 (2018).

105.      Qiao, Y., Sun, J., Ding, Y., Le, G. & Shi, Y. Alterations of the gut microbiota in high-fat diet mice is strongly linked to oxidative stress. Appl. Microbiol. Biotechnol. 97, 1689–97 (2013).

106.      Xu, J. et al. Regulation of an antioxidant blend on intestinal redox status and major microbiota in early weaned piglets. Nutrition 30, 584–9 (2014).

107.      Xu, C. C. et al. Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets. J. Anim. Sci. 92, 1504–11 (2014).

108.      Rivera-Chávez, F., Lopez, C. A. & Bäumler, A. J. Oxygen as a driver of gut dysbiosis. Free Radic. Biol. Med. 105, 93–101 (2017).

109.      Yanaka, A., Kakinoki, N. & Yamamoto, T. 1103 – Daily Intake of Sulforaphane-Rich Broccoli Sprouts Improves Bowel Habits in Human Subjects, by Strengthening Nrf2-Dependent Anti-Oxidant Systems and by Normalizing Gut Microbiota. Gastroenterology 156, S-235 (2019).

110.      Cai, J. et al. Inhibition of influenza infection by glutathione. Free Radic. Biol. Med. 34, 928–36 (2003).

111.      Paiva, C. N. & Bozza, M. T. Are reactive oxygen species always detrimental to pathogens? Antioxid. Redox Signal. 20, 1000–37 (2014).

112.      Sgarbanti, R. et al. Redox regulation of the influenza hemagglutinin maturation process: a new cell-mediated strategy for anti-influenza therapy. Antioxid. Redox Signal. 15, 593–606 (2011).

113.      Checconi, P. et al. The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State. Int. J. Mol. Sci. 14, 4148–62 (2013).

114.      De Flora, S., Grassi, C. & Carati, L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur. Respir. J. 10, 1535–41 (1997).

115.      Beck, M. A. Selenium and vitamin E status: impact on viral pathogenicity. J. Nutr. 137, 1338–40 (2007).

116.      Fraternale, A. et al. Effect of the N-butanoyl glutathione (GSH) derivative and acyclovir on HSV-1 replication and Th1 cytokine expression in human macrophages. Med. Microbiol. Immunol. 203, 283–9 (2014).

117.      Palamara, A. T. et al. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res. 27, 237–53 (1995).

118.      Wu, Y.-H. et al. Glucose-6-phosphate dehydrogenase deficiency enhances human coronavirus 229E infection. J. Infect. Dis. 197, 812–6 (2008).

119.      Cheng, M.-L., Weng, S.-F., Kuo, C.-H. & Ho, H.-Y. Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication. PLoS One 9, e113234 (2014).

120.      Ho, H.-Y. et al. Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection. J. Gen. Virol. 89, 2080–9 (2008).

121.      Lassoued, S., Gargouri, B., El Feki, A. el F., Attia, H. & Van Pelt, J. Transcription of the Epstein-Barr virus lytic cycle activator BZLF-1 during oxidative stress induction. Biol. Trace Elem. Res. 137, 13–22 (2010).

122.      Mikirova, N. & Hunninghake, R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med. Sci. Monit. 20, 725–32 (2014).

123.      Noah, T. L. et al. Effect of broccoli sprouts on nasal response to live attenuated influenza virus in smokers: A randomized, double-blind study. PLoS One 9, (2014).

124.      Lee, C. Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid. Med. Cell. Longev. 2018, (2018).

125.      Liu, Q., Gao, Y. & Ci, X. Role of Nrf2 and Its Activators in Respiratory Diseases. Oxid. Med. Cell. Longev. 2019, 7090534 (2019).

126.      Wyler, E. et al. Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program. Nat. Commun. 10, 4878 (2019).

127.      Gunderstofte, C. et al. Nrf2 Negatively Regulates Type I Interferon Responses and Increases Susceptibility to Herpes Genital Infection in Mice. Front. Immunol. 10, 2101 (2019).

128.      Akuta, T., Zaki, M. H., Yoshitake, J., Okamoto, T. & Akaike, T. Nitrative stress through formation of 8-nitroguanosine: Insights into microbial pathogenesis. Nitric Oxide - Biol. Chem. 14, 101–108 (2006).

129.      Seronello, S. et al. Ethanol and reactive species increase basal sequence heterogeneity of hepatitis C virus and produce variants with reduced susceptibility to antivirals. PLoS One 6, e27436 (2011).

130.      Azenabor, A. A., Muili, K., Akoachere, J.-F. & Chaudhry, A. Macrophage antioxidant enzymes regulate Chlamydia pneumoniae chronicity: evidence of the effect of redox balance on host-pathogen relationship. Immunobiology 211, 325–39 (2006).

131.      Yanaka, A. et al. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev. Res. (Phila). 2, 353–60 (2009).

132.      Deramaudt, T. B., Ali, M., Vinit, S. & Bonay, M. Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation. Int. J. Mol. Med. (2020). doi:10.3892/ijmm.2020.4563

133.      Riedelberger, M. et al. Type I Interferon Response Dysregulates Host Iron Homeostasis and Enhances Candida glabrata Infection. Cell Host Microbe 27, 454-466.e8 (2020).