Role of glutathione metabolism in host defense against Borrelia burgdorferi infection

Abstract

Pathogen-induced changes in host cell metabolism are known to be important for the immune response. In this study, we investigated how infection with the Lyme disease-causing bacterium () affects host metabolic pathways and how these metabolic pathways may impact host defense. First, metabolome analysis was performed on human primary monocytes from healthy volunteers, stimulated for 24 h with at low multiplicity of infection (MOI). Pathway analysis indicated that glutathione (GSH) metabolism was the pathway most significantly affected by Specifically, intracellular levels of GSH increased on average 10-fold in response to exposure. Furthermore, these changes were found to be specific, as they were not seen during stimulation with other pathogens. Next, metabolome analysis was performed on serum samples from patients with early-onset Lyme disease in comparison with patients with other infections. Supporting the in vitro analysis, we identified a cluster of GSH-related metabolites, the γ-glutamyl amino acids, specifically altered in patients with Lyme disease, and not in other infections. Lastly, we performed in vitro experiments to validate the role for GSH metabolism in host response against We found that the GSH pathway is essential for -induced cytokine production and identified glutathionylation as a potential mediating mechanism. Taken together, these data indicate a central role for the GSH pathway in the host response to GSH metabolism and glutathionylation may therefore be important factors in the pathogenesis of Lyme disease and potentially other inflammatory diseases as well.

Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response

“…This enzyme is present in B. burgdorferi OMVs, making it a prime candidate for modulation of host cell superoxide levels [18]. Past studies have shown that B. burgdorferi can reduce peripheral blood mononuclear cell ROS levels in response to ROS-generating stimuli, while at the same time showing a decrease in intracellular superoxide [55]. In the same study, it was found that the decrease in superoxide was independent of mammalian antioxidants, namely glutathione.…”

Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases

“…Glutathione and alkalizing the body to decrease acidic byproducts has been shown to be helpful in decreasing symptomatology in this population of patients [57]. Glutathione metabolism has also been discovered to be the most important target of B. burgdorferi infection, and this pathway is essential for cytokine production, likely through glutathionylation [58]. Glutathione and GSH precursors (NAC) with antioxidants that help regenerate GSH (alpha lipoic acid) have been an effective mainstay of treating cytokine storms and Herxheimer reactions in our tick-borne population for decades [59,60].…”

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

“…Glutathione modulates inflammation [172,173]. A 2018 PNAS report found that intracellular GSH production was increased up to 10-fold during an infection with Borrelia burgdorferi , and infection was a key factor in inflammation/cytokine production [174]. Glutathione is also a key factor in helping to detoxify environmental chemicals.…”