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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), is responsible for causing significant morbidity and mortality, especially among individuals with compromised immune systems. We have previously shown that the supplementation of liposomal glutathione (L-GSH) reduces M. tb viability and enhances a Th-1 cytokine response, promoting granuloma formation in human peripheral blood mononuclear cells in vitro. However, the effects of L-GSH supplementation in modulating the immune responses in the lungs during an active M. tb infection have yet to be explored. In this article, we report the effects of L-GSH supplementation during an active M. tb infection in a mouse model of pulmonary infection. We determine the total GSH levels, malondialdehyde (MDA) levels, cytokine profiles, granuloma formation, and M. tb burden in untreated and L-GSH-treated mice over time. In 40 mM L-GSH-supplemented mice, an increase in the total GSH levels was observed in the lungs. When compared to untreated mice, the treatment of M. tb-infected mice with 40 mM and 80 mM L-GSH resulted in a reduction in MDA levels in the lungs. L-GSH treatment also resulted in a significant increase in the levels of IL-12, IFN-γ, IL-2, IL-17, and TNF-α in the lungs, while down-regulating the production of IL-6, IL-10, and TGF-β in the lungs. A reduction in M. tb survival along with a decrease in granuloma size in the lungs of M. tb-infected mice was observed after L-GSH treatment. Our results show that the supplementation of mice with L-GSH led to increased levels of total GSH, which is associated with reduced oxidative stress, increased levels of granuloma-promoting cytokines, and decreased M. tb burden in the lung. These results illustrate how GSH can help mitigate M. tb infection and provide an insight into future therapeutic interventions.

Details

Title
Liposomal Glutathione Helps to Mitigate Mycobacterium tuberculosis Infection in the Lungs
Author
Nala Kachour 1 ; Beever, Abrianna 1 ; Owens, James 2 ; Cao, Ruoqiong 2 ; Kolloli, Afsal 3   VIAFID ORCID Logo  ; Kumar, Ranjeet 3   VIAFID ORCID Logo  ; Sasaninia, Kayvan 1   VIAFID ORCID Logo  ; Vaughn, Charles 1   VIAFID ORCID Logo  ; Singh, Mohkam 1 ; Truong, Edward 1 ; Khatchadourian, Christopher 2 ; Sisliyan, Christina 2 ; Zakery, Klara 2 ; Khamas, Wael 4 ; Selvakumar Subbian 3   VIAFID ORCID Logo  ; Venketaraman, Vishwanath 5   VIAFID ORCID Logo 

 Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] (N.K.); [email protected] (A.B.); [email protected] (K.S.); [email protected] (C.V.); [email protected] (M.S.); [email protected] (E.T.) 
 College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] (J.O.); [email protected] (R.C.); [email protected] (C.K.); [email protected] (C.S.); [email protected] (K.Z.) 
 Public Health Research Institute Center, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA; [email protected] (A.K.); [email protected] (R.K.); [email protected] (S.S.) 
 College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] 
 Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] (N.K.); [email protected] (A.B.); [email protected] (K.S.); [email protected] (C.V.); [email protected] (M.S.); [email protected] (E.T.); College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] (J.O.); [email protected] (R.C.); [email protected] (C.K.); [email protected] (C.S.); [email protected] (K.Z.) 
First page
673
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
20763921
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2652951178
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.