Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, partly due to the prolonged duration and toxicity of standard antibiotic regimens. Adjunctive therapies that enhance antimicrobial efficacy and modulate host immunity are urgently needed. Curcumin, a natural bioactive compound derived from Curcuma longa, possesses broad therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and antiviral effects. This study evaluated the effects of curcumin in combination with first- and second-line antibiotics against Mtb in both in vitro and in vivo models. Our results demonstrated that curcumin exerts direct antibacterial activity against both the drug-sensitive H37Rv strain and a multidrug-resistant (MDR) clinical isolate. Furthermore, curcumin synergized with conventional antibiotics, enhancing bacterial clearance in infected macrophages while promoting the production of IL-12, a key cytokine in protective immune responses. In a murine model of progressive pulmonary TB, combination therapy with curcumin and first-line antibiotics significantly reduced the lung bacterial burden and improved behavioral outcomes compared to antibiotic treatment alone. These findings suggest that curcumin acts through both direct antimicrobial mechanisms and immune modulation, supporting its potential as an adjunctive therapy agent for TB. Future studies should focus on optimizing curcumin formulation, dosing, and bioavailability to facilitate the clinical translation of this compound.

Tuberculosis (TB) is the deadliest disease caused by a bacterial agent. Glucocorticoids (GCs) have a typical anti-inflammatory effect, but recently it has been shown that they can present proinflammatory activity, mainly by increasing molecules from innate immunity. In the current study, we evaluated the effect of low doses of dexamethasone on Mycobacterium tuberculosis in vivo and in vitro. We used an established mice model of progressing tuberculosis (TB) in the in vivo studies. Intratracheal or intranasal dexamethasone therapy administered with conventional antibiotics in the late stage of the disease decreased the lung bacilli load and lung pneumonia, and increased the survival of the animals. Finally, the treatment decreased the inflammatory response in the SNC and, therefore, sickness behavior and neurological abnormalities in the infected animals. In the in vitro experiments, we used a cell line of murine alveolar macrophages infected with Mtb. Low-dose dexamethasone treatment increased the clearance capacity of Mtb by MHS macrophages, MIP-1α, and TLR2 expression, decreased proinflammatory and anti-inflammatory cytokines, and induced apoptosis, a molecular process that contributes to the control of the mycobacteria. In conclusion, the administration of low doses of dexamethasone represents a promising adjuvant treatment for pulmonary TB.

Tuberculosis (TB), caused primarily by Mycobacterium tuberculosis (Mtb), remains a major global health challenge and the leading cause of death worldwide from a single infectious agent. In developed countries, TB is a prototypical re-emerging infectious disease, while in developing nations, it is a devastating health issue. In humans and mice, cell-mediated immunity, driven by T lymphocytes, plays a crucial role in coordinating and regulating the immune response to eliminate Mtb. Significant evidence indicates that CD4+ T helper lymphocytes (Th-1 cells) and Th-17 cells are vital to the protective immune response against Mtb. CD4+ Th-1 cells activate macrophages, enhancing their ability to eliminate mycobacteria. They also recruit additional immune cells to infection and inflammation sites and promote the cytotoxicity of CD8+ T lymphocytes, which are essential for killing infected cells through apoptosis. Indeed, the immune response to Mtb involves a carefully balanced interaction between protective inflammation and tissue-damaging pathology. Therefore, the involvement of anti-inflammatory cells, such as Th-2 lymphocytes and T regulatory cells, is also critical in modulating and controlling inflammation that can cause tissue damage. In this chapter, the roles of various T-lymphocyte subtypes in the immune response to Mtb are discussed, along with the different T-cell immune evasion strategies Mtb employs to prevent clearance. Additionally, novel immunotherapeutic approaches aimed at enhancing protective T-cell activity or suppressing harmful T-cell effects are explored, providing potential methods to facilitate pathogen eradication and reduce the lengthy chemotherapy required for this significant infectious disease.