Assessment of the immunomodulatory effects of heat-killed Mycobacterium aurum on THP-1 monocyte to macrophage differentiation and on THP-1 macrophage polarization

Abstract

Heat killed (HK) mycobacterial preparations have been previously reported to hold immunomodulatory properties and have demonstrated an encouraging therapeutic potential. HK Mycobacterium aurum (M. aurum) is currently undergoing clinical development whereby its immunotherapeutic and immunomodulatory effects are unknown. Here, we studied the in vitro immunomodulatory effects of HK M. aurum on THP-1 monocytes and on THP-1derived macrophages (Ms) in terms of its ability to induce monocyte to M differentiation and M polarization. HK M. aurum failed to induce the differentiation of THP-1 monocytes into M0-Ms and showed similar features (non-adherence, low granularity, and low CD11b/CD11c expression). Of note M. aurum treatment of M0-Ms induced their expression of M1-M-associated surface markers (CD40, CD80, and HLA-DR). On the other hand, M. aurum-treated M0-Ms showed little to no expression of M2-M-associated surface markers (CD36, CD163, CD206, and CD209). Additionally, HK M. aurum-treated M0-Ms secreted significant amounts of the pro-inflammatory (M1 associated) cytokines (IL-6, IL-12p40, TNF- and CCL4) and anti-inflammatory cytokines (IL-10 and CCL22). However, the levels of cytokines and chemokines produced by M. aurum-treated M0-Ms were significantly different from those produced by M2-Ms. Finally, M. aurum treatment of M0-Ms did not cause any significant change in their endocytosis capacity. Collectively, our data suggests that HK M. aurum can polarize M0-Ms towards an M1-like M phenotype; however, it is incapable of driving the differentiation of THP-1 monocytes into Ms. Biological findings from this study improved our current understanding about the outcome of interaction of HK mycobacteria with human innate immune cells.