期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 311, 期 1, 页码 G130-G141出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00461.2014
关键词
muscarinic receptor; Nippostrongylus brasiliensis; T(H)2 cytokines; mucosal homeostasis; host defense
资金
- National Institutes of Health [R01-A1/DK-049316, R01-DK-083418, USDA/ARS 1235-51000-055]
- NIH [T32-DK-067872, P30-DK-090868]
- ARS [ARS-0426497, 813602] Funding Source: Federal RePORTER
Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient (Chrm3(-/-)) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the T(H)2-eliciting enteric nematode N. brasiliensis. Intestinal permeability and expression of T(H)1/T(H)17 cytokines were increased in uninfected Chrm3(-/-) small intestine. Notably, in Chrm3(-/-) mice infected with N. brasiliensis, small intestinal upregulation of T(H)2 cytokines was attenuated and nematode clearance was delayed. In Chrm3(-/-) mice, T(H)2-dependent changes in small intestinal function including smooth muscle hypercontractility, increased epithelial permeability, decreased epithelial secretion and absorption, and goblet cell expansion were absent despite N. brasiliensis infection. These findings identify an important role for M3R in host defense and clearance of N. brasiliensis, and support the expanding role of cholinergic muscarinic receptors in maintaining mucosal homeostasis.
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