Host genetic polymorphisms, immune response, and susceptibility to pleural tuberculosis: A systematic review

Background Pleural tuberculosis is one of the most frequent extrapulmonary manifestations of Mycobacterium tuberculosis infection and is characterized by a pronounced immune-mediated response with a low bacillary burden. Host genetic factors appear to play a central role in its immunopathogenesis. Methods A systematic review was conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO (CRD420251051395). Searches were performed across MEDLINE/PubMed, Embase, and SciELO databases, covering publications from 1970 to December 2023. The search strategy combined terms related to pleural involvement, tuberculosis, and genetic polymorphisms. Results Eight studies fulfilled all eligibility criteria. Polymorphisms in genes involved in innate immunity (SLC11A1/NRAMP1, TLR2, TLR4), cytokine regulation (IFN-γ, IL-10), and host lipid metabolism (CYP7A1) were associated with susceptibility patterns and distinct immunological phenotypes in pleural tuberculosis. These findings underscore the multifactorial nature of pleural disease, driven by complex interactions among genetic determinants and immune pathways. Conclusions Available evidence suggests that pleural tuberculosis reflects genetically mediated amplification of innate and adaptive inflammatory responses, particularly involving macrophage activation pathways and Th1-type cytokine signaling. Integration of genomic, transcriptomic, and immunological data may contribute to improved diagnostic precision, risk stratification, and the development of host-directed biomarkers and personalized therapeutic strategies.