Wnt5a Deficiency Regulates Inflammatory Cytokine Secretion, Polarization, and Apoptosis in Mycobacterium tuberculosis-Infected Macrophages

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (MTB), is one of the global public health catastrophes. Wnt signaling has recently been identified to exert immunoregulatory functions in a variety of inflammatory and infectious diseases, including tuberculosis. The opposite expression of Wnt5a in human and mice during MTB infection drives us to explore the roles and biological significances of reduced Wnt5a for MTB-treated mice. In our study, the reduction of WNT5A in MTB-treated mice lung tissues or MTB-infected mice bone marrow-derived macrophages (BM-Mo) was in a dose- and time-dependent manner. Then, WNT5A-silenced mice, secreted frizzled-related protein 1 (SFRP1)-overexpressed or -silenced mice BM-Mo, were constructed to regulate Wnt5a levels. When Wnt5a is deficient, MTB-induced increases of pro-inflammatory cytokines (TNF-α, IL-1β, IL-12, and IL-6) can be markedly attenuated in mice lung tissues or BM-Mo. Besides, external disturbance triggered that Wnt5a lower expression ca...