Effects of Mycobacterium vaccae on toll-like receptor expression

Abstract

Rationale Toll-like receptors (TLRs), transmembrane proteins expressed on the surface of antigen presenting cells (APCs), contribute to the activation of the innate immune system by recognizing specific pathogen-associated molecular patterns and by directing T cell responses. For example schistosomal lysophosphatidylserine stimulation of dendritic cells (DCs) drives the development of regulatory T cells (Tregs). Since Mycobacterium vaccae has similarly been found to induce Tregs and to improve symptoms of pulmonary allergic inflammation, we investigated its effects on the expression of TLRs to assess their involvement in the bacterium's mode of action. Methods Using real-time PCR, TLRs and cytokine expression were measured from both M. vaccae-stimulated pulmonary CD11c+ APCs from allergic mice and from M. vaccae-stimulated THP-1 cells. We determined the expression of TLR2, -4, -7 and -8 and of CD14, a surface molecule involved in mediating TLR signaling. Results M. vaccae differentially influenced the expression of TLRs both in vitro and in vivo. For example, expression of TLR2 and CD14 was increased in both stimulated THP-1 cells and pulmonary CD11c+ cells. Moreover, TLR2 increased expression in this CD11c+ population correlates with an increased expression of the regulatory cytokines IL-10 and IFN-α. Conclusions These results suggest that stimulation with M. vaccae influences the expression of TLRs on APCs, thereby directing the host's immune responses. It could be speculated that M. vaccae-induced CD11c+ cells have a potential regulatory role through their secretion of immunomodulatory cytokines that are TLRs-dependent.