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-M phi) was in a dose-and time-dependent manner. Then, WNT5A-silenced mice, secreted frizzled-related protein 1 (SFRP1)-overexpressed or -silenced mice BM-M phi, were constructed to regulate Wnt5a levels. When Wnt5a is deficient, MTB-induced increases of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-12, and IL-6) can be markedly attenuated in mice lung tissues or BM-M phi. Besides, external disturbance triggered that Wnt5a lower expression can induce M phi to be M2 phenotype and enhance cell apoptosis of MTB-infected mice BM-M phi. Hence, the reduction of Wnt5a is a tactful strategy adopted by M phi to resistant MTB-induced immune responses and to enhance MTB-induced M phi apoptosis in mice. Our study revealed a new style for M phi to manipulate themselves against MTB infection. Our research identifies that Wnt5a deficiency can regulate inflammatory cytokine secretion, polarization, and apoptosis in MTB-infected M phi.