IL-17's Dual Role in Tuberculosis Protection and Pathogenesis Depends on Context

Despite significant advances, tuberculosis (TB) remains a leading cause of death globally, necessitating novel therapeutic and vaccine strategies. Current treatments face challenges like drug resistance and prolonged regimens, highlighting the urgent need for host-directed therapies. Interleukin-17 (IL-17) is a cytokine with a perplexing dual nature in TB immunity: it's consistently identified as a key player in protective immune responses, yet also implicated as a major driver of the immunopathology that contributes to TB morbidity and mortality. This review addresses this critical conundrum, aiming to synthesize the complex arguments surrounding IL-17's role.

This comprehensive review article synthesizes existing literature to address the paradoxical roles of IL-17 in tuberculosis (TB). The authors systematically examined studies supporting IL-17's involvement in both protective immunity and disease pathogenesis. Their approach involved analyzing immune correlates of protection from natural infection and vaccine-induced responses, alongside evidence linking IL-17 to immunopathology. The review aims to provide a unified perspective on how the context of IL-17 activity dictates its beneficial or detrimental impact in human TB.

The review highlights that IL-17 exhibits context-specific roles in tuberculosis (TB). On one hand, numerous studies consistently identify IL-17 responses as crucial for natural and vaccine-induced protection against Mycobacterium tuberculosis infection and disease progression. These protective roles often involve the recruitment of neutrophils and other immune cells, as well as the induction of antimicrobial peptides. Conversely, IL-17 has also been strongly implicated as a primary driver of the immunopathology underlying TB morbidity and mortality. This detrimental role can manifest through excessive inflammation, tissue damage, and the formation of granulomas that contribute to disease severity. The authors conclude that the precise balance and timing of IL-17 signaling, along with the specific immune microenvironment, dictate whether it acts as a protective or pathogenic factor.

The ultimate impact of IL-17 in human TB is likely to depend on the specific immunological and clinical context.