Role of Th1/Th17 balance regulated by T-bet in a mouse model of Mycobacterium avium complex disease.


Th1 immune responses are thought to be important in protection against intracellular pathogens. T-bet is a critical regulator for Th1 cell differentiation and Th1 cytokine production. The aim of this study was to determine the role of T-bet in host defense against Mycobacterium avium complex (MAC) infection. Wild-type mice, T-bet-deficient mice, and T-bet-overexpressing mice were infected with MAC via intratracheal inoculation. Macrophages and dendritic cells obtained from these mice were incubated with MAC. T-bet-deficient mice were highly susceptible to MAC, compared with wild-type mice and T-bet-overexpressing mice. Neutrophilic pulmonary inflammation was also enhanced in T-bet-deficient mice, but attenuated in T-bet-overexpressing mice, following MAC infection. Cytokine expression shifted toward Th1 in the lung and spleen of T-bet-overexpressing mice, but toward Th17 in T-bet-deficient mice. IFN-γ supplementation to T-bet-deficient mice reduced systemic MAC growth but did not reduce pulmonary inflammation. In contrast, neutralization of IL-17 in T-bet-deficient mice reduced pulmonary inflammation but did not affect mycobacterial growth in any organs tested. T-bet-deficient T cells tended to differentiate toward Th17 cells in vitro following exposure to MAC. Treatment with NO donor suppressed MAC-induced Th17 cell differentiation of T-bet-deficient T cells. This study identified that the fine balance between Th1 and Th17 responses is essential in defining the outcome of MAC disease. T-bet functions as a regulator for Th1/Th17 balance and is a critical determinant for host resistance to MAC infection by controlling cytokine and NO levels.

DOI: 10.4049/jimmunol.1302258

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@article{Matsuyama2014RoleOT, title={Role of Th1/Th17 balance regulated by T-bet in a mouse model of Mycobacterium avium complex disease.}, author={Masashi Matsuyama and Yukio Ishii and Yuichi Yageta and Shigeo Ohtsuka and Satoshi Ano and Yosuke Matsuno and Yuko Morishima and Keigyou Yoh and Satoru Takahashi and Kenji Ogawa and Cory M. Hogaboam and Nobuyuki Hizawa}, journal={Journal of immunology}, year={2014}, volume={192 4}, pages={1707-17} }