Mesenchymal-epithelial Transition Factor Regulates Monocyte Function during Mycobacterial Infection via Indoleamine 2,3-dioxygenase

Abstract

Objective

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), causes an estimated 1.6 million human deaths annually, but the pathogenesis of TB remains unclear. Immunity plays a critical role in the onset and outcome of TB. This study aimed to uncover the roles of innate and adaptive immunity in TB.

Methods

The gene expression profiles generated by RNA sequencing from human peripheral blood mononuclear cells (PBMCs) stimulated with or without Mtb strain H37Rv antigens were analyzed. A total of 973 differentially expressed mRNAs were identified.

Results

The differentially expressed genes were enriched in innate immunity signaling functions. The mesenchymal-epithelial transition factor (MET) gene was significantly upregulated in CD14⁺ monocytes. A MET inhibitor improved the uptake of the BCG strain by monocytes and macrophages as well as inhibited the expression of indoleamine 2,3-dioxygenase (IDO). The expression of IDO was increased in PBMCs stimulated with Mtb antigens, and the IDO inhibitor promoted the expression of CD40, CD83, and CD86.

Conclusion

Our results might provide clues regarding the immunomodulatory mechanisms used by Mtb to evade the host defense system.

Keywords

monocytes / mycobacteria / mesenchymal-epithelial transition factor / indoleamine 2,3-dioxygenase

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