Significant reduction of granulomas in Nrf2-deficient mice infected with Mycobacterium tuberculosis.
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 weeks. As disruption of Nrf2 promotes immune cells that stimulate Th2-like immunoresponsiveness, Nrf2-deficient mice may be resistant to M. tuberculosis infection.


METHODS
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.


CONCLUSIONS
It is concluded that Nrf2 inversely regulates M. tuberculosis-induced granuloma development at the late stage.
The Research Institute of Tuberculosis, Tokyo 204-0022, Japan.
S
S
Mizuno
M
M
Yamamoto
I
I
Sugawara
D000818:Animals; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology*; D018793:Interleukin-13 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D051267:NF-E2-Related Factor 2 / Q000172:deficiency*; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D018793:Interleukin-13; D007376:Interleukin-2; D051267:NF-E2-Related Factor 2