Uncovering the in vitro immunomodulatory actions of heat-killed mycobacterium aurum on primary human monocytes and neutrophils

Abstract

Manipulation of innate immune cells constitutes one mechanism through which the host’s immune system can be shaped and subsequently directed towards appropriate and beneficial immune responses. Numerous studies have demonstrated the immune regulatory capacity of heat-killed (HK) mycobacteria, a characteristic that has been mainly attributed to their complex cell wall composition. Due to their immunomodulatory effects, HK mycobacteria have been widely evaluated in clinical trials conducted in multiple disease settings whereby these trials confirmed their immunotherapeutic potential. A HK whole cell preparation of Mycobacterium aurum (M. aurum) has recently gotten much attention as a potential immunomodulatory agent; however, its effects on human primary innate immune cells have not been yet investigated. Therefore, this study assessed by flow cytometry the effect of in vitro whole blood stimulation with HK M. aurum on the surface expression of a panel of immunologically-relevant receptors on neutrophils and monocytes as well as on reactive oxygen species (ROS) production by both innate immune cell types. Our data showed a significant increase in the expression of adhesion receptors, CD11a, CD11b and CD18 on monocytes, and CD11b and CD18 on neutrophils after whole blood stimulation with HK M. aurum. In addition, the CR, CD35, showed a significant upregulated expression on M. aurum-stimulated monocytes and neutrophils, while a significant elevation in FcγRI (CD64) expression on neutrophils was noted in response to HK M. aurum stimulation. Stimulation of whole blood with HK M. aurum did not significantly alter ROS generation by monocytes and neutrophils. In conclusion, our data revealed an immunomodulatory effect of HK M. aurum on primary human monocytes and neutrophils through regulating the expression of different types of surface receptors. This study showed a promising immunomodulatory effect for HK M. aurum, hence additional studies are required to comprehensively understand the precise mechanism of action of HK M. aurum and better characterize the outcome of interaction between HK mycobacteria and human innate immune cells.