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

The Research Institute of Tuberculosis, Tokyo 204-0022, Japan.
The Indian journal of tuberculosis 04/2010; 57(2):108-13.
Source: PubMed


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 weeks. As disruption of Nrf2 promotes immune cells that stimulate Th2-like immunoresponsiveness, Nrf2-deficient mice may be resistant to M. tuberculosis infection.
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.
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.
It is concluded that Nrf2 inversely regulates M. tuberculosis-induced granuloma development at the late stage.

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    • "Nrf2- knock out animals are not only over-sensitive to oxidative stress but also their microglial cells are hyper-inflammatory and the animals develop white matter damage spontaneously (Hubbs et al. 2007). Nrf2-deficient mice show an increased susceptibility to airway inflammation and when infected with M. tuberculosis show increased expression of IL-2 and IL-13 mRNA (Mizuno et al. 2010). Tert-butylhydroquinone , which activates Nrf2, induces IL-10 (Boyle et al. 2011). "
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