Context-specific roles for IL-17 in tuberculosis

The number 17 is considered unlucky by some Italians as its Roman numerals - XVII - can be rearranged as Vixi, a Latin expression that can be interpreted as "my life is over". In other contexts, the number 17 is associated with wisdom and success. This paradox holds true when it comes to the role of interleukin 17 (IL-17) in tuberculosis (TB). On one hand, immune correlates of protection studies have consistently identified IL-17 responses as key players in natural and vaccine induced protection against infection and disease. On the other, IL-17 has been proposed as a main driver of the immunopathology that underlies TB morbidity and mortality. Thus, while some researchers seek to develop novel TB vaccine approaches that promote IL-17 responses, others hunt for host-directed therapeutic approaches that block its activity. In this article, we attempt to address this conundrum and synthesise the main arguments supporting a role for IL-17 in the protection and pathogenesis of this deadly human infectious disease. Ultimately, as with superstition, whether the 17th interleukin is friend or foe in human TB is likely to depend on the context.