Lipoteichoic acid downregulates FcepsilonRI expression on human mast cells through Toll-like receptor 2.

Abstract

BACKGROUND:

FcepsilonRI 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 FcepsilonRI.

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 FcepsilonRI 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 FcepsilonRI expression and IgE-induced degranulation. None of the bacterial components affected the expression of other Fc receptors, such as Fcgamma receptors or Fcalpha receptor I.

CONCLUSIONS:

Our results indicate that LTA reduces the surface expression of FcepsilonRI 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.

• Authors: Mino Yoshioka, Nobuyuki Fukuishi, Sayuri Iriguchi, Kanae Ohsaki, Hiroyuki Yamanobe, Asumi Inukai, Daisuke Kurihara, Naoki Imajo, Yumiko Yasui, Nobuaki Matsui, Tadayuki Tsujita, Akihiro Ishii, Tsukasa Seya, Makoto Takahama, Masaaki Akagi
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 120 Issue 2 Pg. 452-61 (Aug 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17481719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Lipopolysaccharides
• Peptidoglycan
• RNA, Messenger
• Receptors, IgE
• Teichoic Acids
• Toll-Like Receptor 2
• Toll-Like Receptors
• lipoteichoic acid

Topics

• Cell Degranulation (drug effects)
• Cell Line
• Cell Membrane (metabolism)
• Dose-Response Relationship, Drug
• Down-Regulation (physiology)
• Humans
• Ligands
• Lipopolysaccharides (administration & dosage, pharmacology)
• Lung (cytology)
• Mast Cells (cytology, metabolism, physiology)
• Peptidoglycan (administration & dosage, pharmacology)
• RNA, Messenger (metabolism)
• Receptors, IgE (genetics, metabolism)
• Teichoic Acids (administration & dosage, pharmacology)
• Toll-Like Receptor 2 (physiology)
• Toll-Like Receptors (metabolism)