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


CONCLUSIONS
By knowing how bacterial components modulate MC function, we can expand our possibilities for therapeutic interventions of allergic diseases.
Yoshioka
Mino
M
Department of Pharmacology Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama Bouji 180, Yamashiro-cho, Tokushima, Japan.
Fukuishi
Nobuyuki
N
Iriguchi
Sayuri
S
Ohsaki
Kanae
K
Yamanobe
Hiroyuki
H
Inukai
Asumi
A
Kurihara
Daisuke
D
Imajo
Naoki
N
Yasui
Yumiko
Y
Matsui
Nobuaki
N
Tsujita
Tadayuki
T
Ishii
Akihiro
A
Seya
Tsukasa
T
Takahama
Makoto
M
Akagi
Masaaki
M
D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010457:Peptidoglycan / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D013682:Teichoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism
D008024:Ligands; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D012333:RNA, Messenger; D017455:Receptors, IgE; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C009900:lipoteichoic acid