Mast cells play a crucial role in Staphylococcus aureus peptidoglycan-induced diarrhea.
Bacterium-induced diarrhea results in 2 to 2.5 million deaths in the world each year. The mechanism needs to be further understood. Staphylococcus aureus infection has a close relation with diarrhea; its cell wall component peptidoglycan (PGN) has strong biological activity on immune cells and possibly plays a role in S. aureus-induced diarrhea. The present study showed that oral PGN-induced diarrhea in mice in a dose-dependent manner. Intestinal epithelial cells absorbed PGN via the intracellular pathway. Intestinal mast cells were activated after PGN gavage. Toll-like receptor (TLR)2 expression was detected in mast cells in the intestine as well as in the murine mast cell line p815 cells. Blocking TLR2 or nucleotide-binding oligomerization domain (NOD)1 with related antibodies or RNA interference abolished PGN-induced p815 cell activation. The mast cell mediator histamine and serotonin had synergistic effects in PGN-induced diarrhea. In summary, oral PGN can induce diarrhea in mice, and TLR2 and NOD1 mediate the PGN-induced mast cell activation that plays a critical role in diarrhea induction. Blockade of TLR2 or NOD1 or treating mice with a mast cell stabilizer can efficiently inhibit PGN-induced-diarrhea, providing potential therapeutic significance.
Feng
Bai-Sui
BS
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
He
Shao-Heng
SH
Zheng
Peng-Yuan
PY
Wu
Linda
L
Yang
Ping-Chang
PC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007424:Intracellular Fluid / Q000378:metabolism; D007665:Ketotifen / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008854:Microscopy, Electron; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D006634:Histamine H1 Antagonists; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D010457:Peptidoglycan; D012702:Serotonin Antagonists; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007665:Ketotifen