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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2021-05-01
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| Series: | Biomolecular Concepts |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/bmc-2021-0003 |
| _version_ | 1828426330289471488 |
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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 | DOAJ |
| 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. |
| first_indexed | 2024-12-10T16:44:41Z |
| format | Article |
| id | doaj.art-c43bbc7fcf82412487931c6f07e9b5b8 |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-10T16:44:41Z |
| publishDate | 2021-05-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-c43bbc7fcf82412487931c6f07e9b5b82022-12-22T01:41:07ZengDe GruyterBiomolecular Concepts1868-50211868-503X2021-05-01121162610.1515/bmc-2021-0003The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 DiabetesTo Kimberly0Cao Ruoqiong1Yegiazaryan Aram2Owens James3Sasaninia Kayvan4Vaughn Charles5Singh Mohkam6Truong Edward7Sathananthan Airani8Venketaraman Vishwanath9Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA; College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USATuberculosis (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.https://doi.org/10.1515/bmc-2021-0003glutathioneimmune responsesmycobacteriacytokineshost-directed therapieseverolimusdiabetes |
| spellingShingle | 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 Biomolecular Concepts glutathione immune responses mycobacteria cytokines host-directed therapies everolimus 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 | glutathione immune responses mycobacteria cytokines host-directed therapies everolimus diabetes |
| url | https://doi.org/10.1515/bmc-2021-0003 |
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