BATF2/SINHCAF regulates the quantity and function of macrophages infected with Mycobacterium Tuberculosis via regulation of TTC23 through Wnt/β-catenin pathway.

Abstract

Elucidating the pathogenic mechanism of Tuberculosis (TB) can contribute to control TB. Basic leucine zipper transcription factor ATF-like 2 (BATF2) belonging to a large family of leucine zipper transcription factors (TFs) termed bZip proteins, had been verified to have important value in the diagnosis of TB. However, its role and mechanism in TB had not been elucidated. The study aimed to explore its function and molecular mechanism in macrophages infected with Mycobacterium tuberculosis (Mtb). The results indicated that BATF2 inhibited cell proliferation, promoted inflammatory response and impaired the antibacterial and antigen-presenting capacity in macrophages for T cells through regulating its downstream gene TTC23 by interacting with SINHCAF. Above roles and regulations were dependent on β-catenin functions in macrophages infected with Mtb. Clinical samples verified that the expressions of BATF2 and TTC23 were significantly higher in the blood of patients with pulmonary TB compared with health controls. Altogether, BATF2 interacted with SINHCAF to regulate the quantity and function of macrophages during Mtb infection by targeting TTC23 through Wnt/β-catenin pathway.