Immune biomarkers as key targets in managing tuberculosis: A systematic review

Tuberculosis remains a major global health challenge and is one of the leading causes of mortality worldwide. In recent years, the resurgence of the disease has intensified research efforts aimed at understanding the host’s immune defence and the pathogenic mechanisms of Mycobacterium tuberculosis infection. It is estimated that approximately one-third of the world’s population is infected with M. tuberculosis , although only around 9 million people develop active TB each year. Among those infected, just 5–10 % will progress to active disease during their lifetime. The objective of this review is to comprehensively examine the multifaceted immune response of the human host to Mycobacterium tuberculosis infection, with a particular focus on both innate and adaptive immune mechanisms that influence disease progression, latency, and reactivation. This study highlights the pivotal roles of macrophages in pathogen recognition, phagocytosis, and cytokine-mediated killing through reactive oxygen and nitrogen intermediates. It also underscores the function of T lymphocytes—especially CD4⁺ and CD8⁺ cells—in granuloma formation, antigen presentation, and cytokine secretion (e.g., IFN-γ, IL-2), which are central to bacterial containment. The review further explores the contributions of natural killer (NK) cells, neutrophils, and unconventional T cells, along with their signaling interactions via cytokines such as IL-12, IL-4, and TNF-α. Additionally, the immunomodulatory influence of vitamin D, the significance of phagolysosomal fusion, and the emerging regulatory role of B cells and antibodies are examined in the context of host defense and vaccine development. By integrating findings from various studies, this review aims to offer a holistic understanding of host-pathogen dynamics and provide insights to inform improved diagnostics, therapeutic strategies, and immune-based interventions against tuberculosis. A literature search was conducted in the scientific database using the keywords " Mycobacterium Tuberculosis , Immune Biomarkers". This review includes a collection of reports from Science Direct, Scholar Google, and PubMed were searched up to 2019. The results were assessed, gathered, and reported in this paper. A total of 180 articles were included, with an exponential growth in the number of articles published from 1987 to 2019. The synthesis of studies from 1987 to 2019 revealed that both innate and adaptive immune responses are essential in TB control. Macrophages and NK cells initiate early defence through phagocytosis and cytokine release. CD4+ and CD8+ T cells contribute to granuloma maintenance and bacterial killing, primarily through IFN-γ and IL-2 production. Immune biomarkers such as nitric oxide, IL-6, and IFN-γ correlate with disease activity. TB immunology reflects a sophisticated interplay between host defense mechanisms and pathogen evasion strategies. While innate immunity initiates the response, adaptive immunity is crucial for long-term control. Macrophages, T cells, cytokines, and recently recognized players like B cells and NK cells shape the outcome of infection. The challenges posed by latent infection, vaccine limitations, and immune evasion highlight the need for novel therapeutic strategies and improved vaccines. A deeper understanding of immune mechanisms and biomarkers could pave the way for more targeted and effective TB interventions.