Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice

This study aimed to investigate the relationship between interleukin (IL)-35 level and IL-35-producing regulatory T cells (iTr35 subset) in Mycobacterium tuberculosis (Mtb)-infected mice. After the mice were injected with Mtb strain H37R via tail vein, the bacterial burden, lung lesions, and the impact of immune suppression on the infected mice were respectively assessed. The results, when compared with the control mice, showed that the mRNA expression levels of the p35 and Epstein-Barr virus-induced gene 3 of IL-35 were significantly increased in the Mtb-infected mouse spleen at 4 or 8 weeks post-infection and their protein expression levels were concurrently increased in the lungs of the mice, especially in 8 week infected mice. In addition, the levels of serum IL-35 and the iTr35 subset in the spleen of mice were also increased in 4 or 8 weeks post-infection compared with the control mice. Importantly, the high bacterial burden and lung lesions and the low mouse weight were found at 8 week post-infection. Therefore, the mice infected with Mtb resulted in elevating IL-35 level and iTr35 subset and increasing bacterial burden and lung lesions. The findings from the study suggest IL-35 and iTr35 cells may exert an immune suppression role in chronic Mtb-infected mice.