## 1 Introduction  
Tuberculosis (TB) is one of the oldest documented infectious diseases in the world. The etiological agent, _Mycobacterium tuberculosis_ (_M. tb), is responsible for causing about 1.2 million deaths and 10 million cases of active disease annually, worldwide [1]. The pathogen is transmitted through inhalation of infectious aerosols, which can allow _M. tb_ to enter the alveoli in the lungs [2]. As an innate immune response to infection, _M. tb_ is internalized by alveolar macrophages via receptor-mediated phagocytosis. However, virulence factors of _M. tb_ prevent phagocytic degradation of the bacteria and ensure its survival in the macrophage, leading to a primary infection [3]. Infected phagocytes migrate into the lung parenchyma and pulmonary lymph nodes, mounting a Th-1 cytokine response that recruits various immune cells to create a granuloma at the site of infection [4]. The granuloma creates a physical barrier and a hypoxic environment that deprives _M. tb_ of nutrients required for its replication, thus suppressing active infection, and localizing the pathogen to the lungs [5; 6]. If the pathogen is not eliminated, _M. tb_ persists in a quiescent state in the granuloma, leading to latent tuberculosis infection (LTBI) [7; 8; 9; 10; 11]. Glutathione (GSH) is an endogenous antioxidant tripeptide composed of glutamate, cysteine, and glycine. The two forms of GSH are reduced GSH (rGSH) and oxidized GSH (GSSG). rGSH is the functional form, containing antioxidant characteristics which prevent cellular damage from reactive oxygen species (ROS). rGSH reacts with ROS, producing GSSG and water, mitigating the ROS and any corresponding potential damage [12; 13]. We have previously reported that GSH is directly toxic to _M. tb_ and can serve as an important effector molecule mediating macrophage control of _M. tb_[14]. Furthermore, GSH augments the function of natural killer (NK) cells and has direct antim mycobacterial activity, thus enhancing immune effects [9; 10]. Immunocompromised individuals, such as those infected with HIV, appear to have decreased GSH levels and thus a compromised defense mechanism against the growth of _M. tb_[9]. However, our previous studies suggest that restoration of GSH in HIV-positive subjects could potentially result in redox homeostasis, cytokine balance and improved immune responses against _M. tb_ infection [11; 12]. Patients with T2 DM exhibit diminished synthesis of GSH-synthesizing enzymes, including the catalytic subunit of glutamine-cysteine ligase (GCLC), and thus produce lower levels of total GSH [9; 13]. T2 DM patients also exhibit increased production of malondialdehydedehyde, a byproduct of lipid peroxidation and a marker for oxidative stress [15; 16]. Patients with T2 DM also have an increase in proinflammatory cytokines and an inadequate Th-1 effector response [16]. Peripheral blood mononuclear cells (PBMCs) isolated from T2 DM patients showed an impaired ability to form granulomas in vitro when infected with Erdman strain _M. tb_ compared to isolates derived from healthy patients [15; 17]. In addition, in vitro _M. tb_ survival and growth in infected PBMCs from T2 DM patients is significantly increased compared to healthy controls [17]. Similar to previous studies performed with HIV-positive patients, supplementation with a liposomal formulation of GSH in T2 DM subjects restored GSH levels and consequently decreased oxidative stress, modulated a Th-1 cytokine response to _M. tb_, and enhanced in vitro granuloma formation and _M. tb_ control [8; 17; 18; 19]. Altogether, these studies suggest that GSH fills important immunomodulatory roles in granuloma formation and in the control of _M. tb_ growth in vitro. However, the effects of GSH deficiency in the lung parenchyma and its impact on the innate and adaptive immune response during an active _M. tb_ infection have yet to be explored. We therefore aim to develop an in vivo mouse model to determine the effects of GSH deficiency on the effector and granulomatous responses against _M.