Lipoteichoic acid downregulates Fcε{lunate}RI expression on human mast cells through Toll-like receptor 2

Background: Fcε{lunate}RI on the surface of mast cells (MCs) plays a central role in allergic responses. Recent evidence shows that exposure to microbial components corresponds with a significant reduction in the risk for allergic diseases. Although many reports suggest that this is due to changes in T-cell functions, how MC functions are altered by bacterial infection remains unknown. Objective: We sought to elucidate the effect of bacterial infection on MC function and expression of Fc receptors, such as Fcε{lunate}RI. Methods: Isolated human pulmonary MCs and a human MC line (LAD2) were stimulated with bacterial components, and the function and surface expression of Fc receptors were measured. Results: Lipoteichoic acid (LTA) and peptidoglycan, but not LPS, flagellin, or 3CpG-oligodeoxynucleotide, reduced the expression of Fcε{lunate}RI on LAD2 cells. An antibody to Toll-like receptor (TLR) 2 partially blocked the effect of LTA but not peptidoglycan. Both LTA and peptidoglycan reduced MC degranulation caused by an antigen-specific IgE. Furthermore, exposure of pulmonary MCs to LTA reduced both Fcε{lunate}RI expression and IgE-induced degranulation. None of the bacterial components affected the expression of other Fc receptors, such as Fcγ receptors or Fcα receptor I. Conclusions: Our results indicate that LTA reduces the surface expression of Fcε{lunate}RI through TLR2 and suggests that TLR2 ligands could be used as a novel therapy for controlling allergic disorders. Clinical implications: By knowing how bacterial components modulate MC function, we can expand our possibilities for therapeutic interventions of allergic diseases.