Published online before print June 28, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061274

Accepted for publication April 30, 2007.

Article

Mast Cells Play a Crucial Role in Staphylococcus aureus Peptidoglycan-Induced Diarrhea

Bai-Sui Feng^*, Shao-Heng He, Peng-Yuan Zheng, Linda Wu^*, and Ping-Chang Yang^*@

From the Department of Pathology,* McMaster University, Hamilton, Ontario, Canada; the Clinical Experimental Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; and the Department of Gastroenterology, the Second Hospital, Zhengzhou University, Zhengzhou, China

^@ To whom correspondence should be addressed. E-mail: yangp{at}mcmaster.ca.

	Abstract

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.