Recent advances in understanding the human host immune response in tuberculous meningitis (TBM) highlight the complex interplay between the immune system and the pathogen, Mycobacterium tuberculosis. TBM, the most severe form of tuberculosis, causes significant mortality and neurological complications despite treatment. The immune response, particularly the innate and adaptive responses, plays a critical role in disease progression and outcomes. Recent studies using proteomics, transcriptomics, and metabolomics have provided new insights into the mechanisms of immune response in TBM, including the entry of M. tuberculosis into the central nervous system (CNS), microglial activation, and the role of various immune cells and pathways. M. tuberculosis can enter the CNS through the blood-brain barrier (BBB) or other CNS barriers, leading to inflammation and immune dysregulation. Microglia, the primary immune cells in the CNS, are infected by M. tuberculosis and release cytokines that contribute to the inflammatory response. The innate immune response involves the activation of inflammasomes, which lead to the production of pro-inflammatory cytokines such as IL-1β and IL-18. The adaptive immune response includes T cells, B cells, and microRNAs, which are crucial for controlling the infection and modulating the immune response. The immune response in TBM is also influenced by the tryptophan pathway, which can contribute to neuroexcitotoxicity through the metabolism of tryptophan into quinolinic acid, an agonist of NMDA receptors. The balance between pro-inflammatory and anti-inflammatory responses is essential for controlling the infection and preventing excessive tissue damage. Host genetic factors also play a role in determining the immune response and outcomes in TBM, with certain polymorphisms associated with increased risk or better outcomes. Despite these advances, challenges remain in understanding the full extent of the immune response in TBM and developing effective host-directed therapies. Further research is needed to explore the role of various immune cells, pathways, and genetic factors in TBM, as well as to develop targeted therapies that can modulate the immune response and improve patient outcomes.Recent advances in understanding the human host immune response in tuberculous meningitis (TBM) highlight the complex interplay between the immune system and the pathogen, Mycobacterium tuberculosis. TBM, the most severe form of tuberculosis, causes significant mortality and neurological complications despite treatment. The immune response, particularly the innate and adaptive responses, plays a critical role in disease progression and outcomes. Recent studies using proteomics, transcriptomics, and metabolomics have provided new insights into the mechanisms of immune response in TBM, including the entry of M. tuberculosis into the central nervous system (CNS), microglial activation, and the role of various immune cells and pathways. M. tuberculosis can enter the CNS through the blood-brain barrier (BBB) or other CNS barriers, leading to inflammation and immune dysregulation. Microglia, the primary immune cells in the CNS, are infected by M. tuberculosis and release cytokines that contribute to the inflammatory response. The innate immune response involves the activation of inflammasomes, which lead to the production of pro-inflammatory cytokines such as IL-1β and IL-18. The adaptive immune response includes T cells, B cells, and microRNAs, which are crucial for controlling the infection and modulating the immune response. The immune response in TBM is also influenced by the tryptophan pathway, which can contribute to neuroexcitotoxicity through the metabolism of tryptophan into quinolinic acid, an agonist of NMDA receptors. The balance between pro-inflammatory and anti-inflammatory responses is essential for controlling the infection and preventing excessive tissue damage. Host genetic factors also play a role in determining the immune response and outcomes in TBM, with certain polymorphisms associated with increased risk or better outcomes. Despite these advances, challenges remain in understanding the full extent of the immune response in TBM and developing effective host-directed therapies. Further research is needed to explore the role of various immune cells, pathways, and genetic factors in TBM, as well as to develop targeted therapies that can modulate the immune response and improve patient outcomes.