Fatima Rahman ^1,2*

• ¹ University College London, London, United Kingdom
• ² Institute for Calculation Applications Mauro Picone, Department of Engineering, ICT and Technology for Energy and Transport, National Research Council (CNR), Rome, Lazio, Italy

Introduction: Tuberculosis remains the leading cause of death from infectious disease among adults worldwide. To date, an overarching review of the immune response to Mtb in humans has not been fully elucidated, with innate immunity remaining poorly understood due to historic focus on adaptive immunity. Specifically, there is a major gap concerning the contribution of the immune system to overall bacterial clearance, specifically residual bacteria. This review aims to describe the time course of interactions between the host immune system and Mtb, from the start of the infection to the development of the adaptive response. Concordantly, we aim to crystallize the pathogenic effects and immunoevasive mechanisms of Mtb. The translational value of animal data is also discussed. Methods: The literature search was conducted in the PubMed, ScienceDirect, and Google Scholar databases, which included reported research from 1990 until 2024. In total, 190 publications were selected and screened, of which 108 were used for abstraction and 86 were used for data extraction. Graphical summaries were created by using the narrative information (i.e., recruitment, recognition, and response) to generate clear visual representations of the immune response at the cellular and molecular levels. Results: The key cellular players included alveolar epithelial cells, neutrophils, natural killer cells, macrophages, dendritic cells, T cells, and granulomatous lesions; and the prominent molecular players included IFN-γ, TNF-α, and IL-10. The paper also sheds light on the immune response to residual bacteria, and applications of the data. Discussion: We provide a comprehensive characterization of the key immune players that are implicated in pulmonary tuberculosis infection, in line with the organs or compartments in which mycobacteria reside, offering a broad vignette of the immune response to Mtb and how it responds to residual bacteria. Ultimately, the data presented could provide immunological insights and optimized criteria to identify efficacious treatment regimens and durations for relapse prevention.