Failure to recruit anti-inflammatory CD103+ dendritic cells and a diminished CD4+ Foxp3+ regulatory T cell pool in mice that display excessive lung inflammation and increased susceptibility to Mycobacterium tuberculosis.

Susceptibility to Mycobacterium tuberculosis is characterized by excessive lung inflammation, tissue damage, and failure to control bacterial growth. To increase our understanding of mechanisms that may regulate the host immune response in the lungs, we characterized dendritic cells expressing CD103 (α(E) integrin) (αE-DCs) and CD4(+) Foxp3(+) regulatory T (T(reg)) cells during M. tuberculosis infection. In resistant C57BL/6 and BALB/c mice, the number of lung αE-DCs increased dramatically during M. tuberculosis infection. In contrast, highly susceptible DBA/2 mice failed to recruit αE-DCs even during chronic infection. Even though tumor necrosis factor alpha (TNF-α) is produced by multiple DCs and macrophage subsets and is required for control of bacterial growth, αE-DCs remained TNF-α negative. Instead, αE-DCs contained a high number of transforming growth factor beta-producing cells in infected mice. Further, we show that T(reg) cells in C57BL/6 and DBA/2 mice induce gamma interferon during pulmonary tuberculosis. In contrast to resistant mice, the T(reg) cell population was diminished in the lungs, but not in the draining pulmonary lymph nodes (PLN), of highly susceptible mice during chronic infection. T(reg) cells have been reported to inhibit M. tuberculosis-specific T cell immunity, leading to increased bacterial growth. Still, despite the reduced number of lung T(reg) cells in DBA/2 mice, the bacterial load in the lungs was increased compared to resistant animals. Our results show that αE-DCs and T(reg) cells that may regulate the host immune response are increased in M. tuberculosis-infected lungs of resistant mice but diminished in infected lungs of susceptible mice.