Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.

Strong, sustained type I IFN signaling intrinsically impairs IFNγ responses in macrophages, increasing susceptibility to tuberculosis in Mycobacterium tuberculosis infection.

• Why it matters: Understanding how type I IFNs weaken immune responses is crucial because they are a major factor in tuberculosis susceptibility, yet the mechanisms remain unclear.
• What they did: The study used genetic elimination of RESIST to block high and sustained type I IFN responses, examining its effect on IFNγ signaling and tuberculosis susceptibility in infected macrophages.
• The result: Blocking persistent type I IFN responses restored IFNγ signaling and reduced tuberculosis susceptibility, revealing that strong, sustained type I IFN responses impair immunity cell-intrinsically.