Basic leucine zipper ATF-like transcription factor involvement in regulating the immune pathogenesis of tuberculosis

Objective To explore the role of basic leucine zipper ATF-like transcription factor (BATF) in active tuberculosis, and to provide clues for diagnosis and therapy of tuberculosis. Methods Sixteen patients with active tuberculosis (ATB), ten cases of latent tuberculosis infection (LTBI) and fourteen healthy controls (HC) were included in this study. Flow cytometry was applied to detect the expressions of BATF and programmed death-1 (PD-1) in T lymphocytes, and the changes of BATF by blockade of PD-1/PD-L pathway using specific blocking antibody antiPD-1, antiPD-L1 and antiPD-L2. The expressions of BATF were compared using Mann-Whitney U test. And the relation of BATF and PD-1 was analyzed using Pearson correlation analysis. Results The CD4+ T lymphocytes expressing BATF accounted for 5.16% (2.96%, 8.71%) of CD4+ T lymphocytes in ATB group, which was higher than 1.05% (0.40%, 1.27%) in LTBI group and 0.71%(0.43%, 1.21%) in HC group, and the difference were statistically significant (U value were 6.5 and 9.0, respectively, both P<0.01). The CD8+ T lymphocytes expressing BATF accounted for 4.10% (2.27%, 8.17%) of CD8+ T lymphocytes in ATB group, which was higher than 0.55% (0.34%, 1.18%) in LTBI group and 0.84% (0.41%, 1.29%) in HC group, and the difference were statistically significant (U value were 5.0 and 8.0, respectively, both P<0.01). Furthermore, the percentage of BATF+ PD-1+ CD4+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 16.0 and 14.5, respectively, both P<0.01), and the percentage of BATF+ PD-1+ CD8+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 10.0 and 16.5, respectively, both P<0.01). In addition, there was a positive correlation between the percentage of BATF+ T cells and PD-1+ T cells, both in CD4+ T cells (r=0.676, P=0.016) and CD8+ T cells (r=0.610, P=0.035). The expressions of BATF both in CD4+ T cells and CD8+ T cells were decreased followed by blockade of PD-1/PD-L pathway (P<0.05). Conclusions BATF may be involved in the regulation of immune pathogenesis of tuberculosis. In order to provide a theory for anti-tuberculosis immunotherapy fargeting BATF, further research need to be proceeded. Key words: BATF; PD-1; Tuberculosis; Immune; T lymphocytes