Tuberculosis as an unconventional interferonopathy.

Tuberculosis is caused by Mycobacterium tuberculosis, a bacterium that accounts for more human mortality than any other. Evidence is accumulating for the view that tuberculosis is an interferonopathy - a disease driven by type I interferons. However, how type I interferons exacerbate tuberculosis remains poorly understood. As an infection, tuberculosis is distinct from conventional interferonopathies, which are autoinflammatory diseases. Here I consider the hypothesis that type I interferons promote bacterial replication by impairing key antibacterial immune responses, including those orchestrated by interleukin-1 and interferon γ. Paradoxically, during tuberculosis, the underlying state of impaired antibacterial immunity co-exists with overt (but ineffective) inflammation. Conceiving of tuberculosis as an unconventional interferonopathy may suggest fruitful avenues for therapeutic intervention.