The Role of Strain Variability in Granuloma Induction and Cough Mechanisms in Tuberculosis Infection

BACKGROUND: Tuberculosis (TB) caused by _Mycobacterium tuberculosis_ (Mtb) remains a major global health concern, especially in low and middle-income countries. Granuloma formation is the hallmark of TB and is defined as organized immune structures designed to limit infection. AIM: This narrative review aims to explore the strain-specific differences in granuloma formation, immune responses, and the mechanism of the cough reflex in TB, with a focus on how these factors contribute to disease progression, transmission, and potential therapeutic strategies METHODOLOGY: A comprehensive literature search was conducted using PubMed, Google Scholar, Cochrane, and ClinicalTrials.gov databases. Studies were selected based on relevance to Mtb strain variation, granuloma morphology, immune response, and cough reflex. RESULTS: Granuloma structure and immunological behaviour differ across several Mtb lineages. Modern TB strains demonstrate increased viral load, induce necrotizing granulomas, and promote persistent cough through mechanical airway irritation and neuroinflammatory pathways. These strains are linked with higher bacterial loads, increased treatment failure, and greater potential for transmission. On the contrary, less virulent strains like H37Ra produce poorly organized granulomas and a weakened immune response. Granulomas near airways exacerbate cough through both mechanical and neuroinflammatory pathways. This kind of immune modulation affects granuloma gene expression, macrophage behavior, and cytokine profiles, influencing the severity of clinical symptoms and potential for transmission. CONCLUSION: Strain-specific differences in Mtb significantly impact granuloma dynamics and cough induction, both of which are crucial to the pathology and transmission of TB. Integrating such diagnostics, host-directed therapies, and targeted vaccines may improve TB control. Further human-based studies are needed to close gaps in understanding how genetic diversity among Mtb strains translates into clinical and epidemiological outcomes.