Assessment of the in vitro differential immunomodulatory effects of heat-killed Mycobacterium aurum, muramyl dipeptide, and lipopolysaccharide on thp-1 monocytes and thp-1-derived m0-macrophages

Abstract

Immunomodulation of the innate immune system can be considered as a novel strategy to regulate the host’s immune response. In particular, the involvement of two innate immune cells, monocytes and macrophages (Ms), is quite pivotal for supporting the host’s capacity to control or combat tumors, microbial infections and autoimmune disorders. Therefore, both innate immune cell subpopulations make them attractive targets for immunomodulators. In this aspect, immunomodulators of bacterial origin such as muramyl dipeptide (MDP), lipopolysaccharide (LPS) and heat-killed (HK) mycobacteria possess structurally miscellaneous pathogen-associated molecular patterns (PAMPs) which can interact with several pattern recognition receptors (PRRs) expressed by innate immune cells. Previous studies have assessed the immunomodulatory effects of MDP and LPS on human monocytes and Ms; however, the immunomodulatory effect of HK Mycobacterium aurum (M. aurum) on both cell types has never been studied. This study primarily aimed to evaluate and compare the effects of MDP, LPS and HK M. aurum on the surface expression levels of a panel of immunologically-relevant receptors on human THP-1 monocytes and THP-1-derived Ms. This panel of cellular receptors constituted members of adhesion molecules (CD11a, CD62L and CD102), co-stimulatory and antigen presentation molecules (CD40, CD80, CD86, HLA-ABC and HLA-DR), PRRs (CD14, CD205 and CD209) and Fc receptors (CD32). Surprisingly, neither short-term (3 h) stimulation of THP-1 monocytes nor prolonged (24 h) stimulation of THP-1 monocytes and THP-1-derived Ms with MDP, LPS or HK M. aurum significantly altered the surface expression of the screened receptors. However, there was trend towards a slight regulation of expression of selected receptors on THP-1 monocytes (CD86 and CD102) and THP-1-derived Ms (CD40 and HLA-DR) following their stimulation with MDP, LPS or HK M. aurum. Moreover, none of the tested immunomodulators affected the viability of THP-1 monocytes and THP-1-derived Ms regardless of the stimulation period. Future studies should address the immunomodulatory effects of the three bacterial-based immunomodulators on human primary monocytes and monocyte-derived Ms.