Tertiary lymphoid structures: protective mechanisms or potential pathogenic roles?

Tuberculosis (TB) accounts for the most deaths amongst humans from an infectious agent. Although the approved vaccines are effective in preventing infant meningitis, they provide inadequate protection for adolescents and adults. There is a need for an improved understanding of immunological determinants of protection from disease as well as the drivers of pathology. Tertiary lymphoid structures (TLS), inducible bronchial-associated lymphoid tissue (iBALT), are an organized accumulation of cells that mount a protective immune response against Mycobacterium tuberculosis (Mtb) in the lung. A comprehensive search of literature was performed in public databases for articles discussing iBALT in TB disease, yielding findings mainly from animal models of pulmonary TB and observational human data. The search revealed a protective role of iBALT characterized by efficient T-cell priming and macrophage activation that restricts Mtb spread. Conversely, dysregulated or chronic TLS formation is associated with excessive cytokine production, myofibroblast activation, autoimmunity, and the progression of post-TB lung disease (PTBLD). Future research must leverage omics technologies to delineate the stromal and immune subsets that govern the protective or pathological iBALT mechanisms.