STAT1 knockout mice are highly susceptible to pulmonary mycobacterial infection

This study was designed to determine the roles of STAT1 protein in defense against mycobacterial infection. Airborne infection of STATI knockout (KO) mice with a Mycobacterium tuberculosis Kurono strain induced multiple necrotic lesions in lungs, spleen and liver, while that in wild-type (WT) mice did not. The STAT1 KO mice succumbed to mycobacterial infection by the 35 th day after infection. Compared with the levels in WT mice, inducible nitric oxide synthase (NOS), tumor necrosis factor-alpha, interferon-gamma and IL-12 mRNA levels were significantly lower in the lung of STATI KO mice. Interestingly, granulomatous lesion development in STAT1 KO mice was inhibited significantly by treatment with exogenous recombinant murine IL-12. Therefore, STATI regulates IL-12 expression and appears to be a critical transcription factor in controling mycobacterial infection.