Lipoteichoic acid downregulates Fc[epsilon]RI expression on human mast cells through Toll-like receptor 2

• Published in: Journal of allergy and clinical immunology 2007-08, Vol.120 (2), p.452
• Main Authors: Yoshioka, Mino, Fukuishi, Nobuyuki, Iriguchi, Sayuri, Ohsaki, Kanae, Yamanobe, Hiroyuki, Inukai, Asumi, Kurihara, Daisuke, Imajo, Naoki, Yasui, Yumiko, Matsui, Nobuaki, Tsujita, Tadayuki, Ishii, Akihiro, Seya, Tsukasa, Takahama, Makoto, Akagi, Masaaki
• Format: Article
• Language: English
• Subjects: Bacterial infections; Genes; Immune system; Ligands; Proteins
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.03.027

Background FcεRI 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 FcεRI. 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 FcεRI 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 FcεRI 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 FcεRI 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.