Significant reduction of granulomas in Nrf2-deficientmice infected with Mycobacterium tuberculosis.

ABSTRACT

Objective: We have reported previously that mice deficient in nuclear erythroid 2 p45-related factor 2 (Nrf2), which regulates the expression of antioxidant and detoxification genes, showed significant susceptibility to airway inflammatory responses when exposed to diesel exhaust particles for eight weeks2. As disruption of Nrf2 promotes immune cells that stimulate Th2-like immunoresponsiveness, Nrf2-deficient mice may be resistant to M. tuberculosis infection. Setting: Nrf2-deficient mice were infected with M. tuberculosis aerially, and the size of their granulomas and cytokine mRNA expression were compared with those of wild-type mice. Results: Significant reduction of granuloma formation and tubercle bacilli in granulomas was noted in the deficient mice 27 weeks after infection, concurrently with higher expression of IL-2 and IL-13 mRNA. Conclusion: It is concluded that Nrf2 inversely regulates M. tuberculosis-induced granuloma development at the late stage.