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The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to h...

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Autores principales: To, Kimberly, Cao, Ruoqiong, Yegiazaryan, Aram, Owens, James, Sasaninia, Kayvan, Vaughn, Charles, Singh, Mohkam, Truong, Edward, Sathananthan, Airani, Venketaraman, Vishwanath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975622/
https://www.ncbi.nlm.nih.gov/pubmed/33966361
http://dx.doi.org/10.1515/bmc-2021-0003
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author To, Kimberly
Cao, Ruoqiong
Yegiazaryan, Aram
Owens, James
Sasaninia, Kayvan
Vaughn, Charles
Singh, Mohkam
Truong, Edward
Sathananthan, Airani
Venketaraman, Vishwanath
author_facet To, Kimberly
Cao, Ruoqiong
Yegiazaryan, Aram
Owens, James
Sasaninia, Kayvan
Vaughn, Charles
Singh, Mohkam
Truong, Edward
Sathananthan, Airani
Venketaraman, Vishwanath
author_sort To, Kimberly
collection PubMed
description Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post- L-GSH/ or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.
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spelling pubmed-89756222022-04-01 The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes To, Kimberly Cao, Ruoqiong Yegiazaryan, Aram Owens, James Sasaninia, Kayvan Vaughn, Charles Singh, Mohkam Truong, Edward Sathananthan, Airani Venketaraman, Vishwanath Biomol Concepts Article Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post- L-GSH/ or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection. 2021-05-09 /pmc/articles/PMC8975622/ /pubmed/33966361 http://dx.doi.org/10.1515/bmc-2021-0003 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License.
spellingShingle Article
To, Kimberly
Cao, Ruoqiong
Yegiazaryan, Aram
Owens, James
Sasaninia, Kayvan
Vaughn, Charles
Singh, Mohkam
Truong, Edward
Sathananthan, Airani
Venketaraman, Vishwanath
The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title_full The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title_fullStr The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title_full_unstemmed The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title_short The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering The Immune Responses Against Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes
title_sort effects of oral liposomal glutathione and in vitro everolimus in altering the immune responses against mycobacterium bovis bcg strain in individuals with type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975622/
https://www.ncbi.nlm.nih.gov/pubmed/33966361
http://dx.doi.org/10.1515/bmc-2021-0003
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