Commensal Bacterial Endocytosis in Epithelial Cells Is Dependent on Myosin Light Chain Kinase–Activated Brush Border Fanning by Interferon-γ

• DOI: 10.1016/j.ajpath.2014.05.003
• Publication Date: 2014-06-07T10:30:38Z
• Authors: Li-Ling Wu; Wei-Hao Peng; Wei-Ting Kuo; Ching-Ying Huang; Yen-Hsuan Ni; Kuo-Shyan Lu; Jerrold R. Turner; Linda C.H. Yu
• Keywords: Internalization; Brush border

Abnormal bacterial adherence and internalization in enterocytes have been documented Crohn disease, celiac surgical stress, intestinal obstruction are associated with low-level interferon (IFN)-γ production. How commensals gain access to epithelial soma through densely packed microvilli rooted on the terminal web (TW) remains unclear. We investigated molecular ultrastructural mechanisms of endocytosis, focusing regulatory roles IFN-γ myosin light chain kinase (MLCK) TW phosphorylation brush border fanning. Mouse intestines were sham operated or obstructed for 6 hours by loop ligation intraluminally administered ML-7 (a MLCK inhibitor) Y27632 Rho-associated inhibitor). After obstruction, endocytosis extraintestinal translocation bacteria observed absence tight junctional damage. Enhanced phosphorylation, arc formation, fanning coincided intermicrovillous penetration, which inhibited neutralizing anti-IFN-γ but not Y27632. The phenomena seen mice genetically deficient long MLCK-210 IFN-γ. Stimulation human Caco-2BBe cells caused MLCK-dependent formation fanning, preceded caveolin-mediated cholesterol-rich lipid rafts. In conclusion, MLCK-activated promotes normally noninvasive enteric bacteria. Transcytotic commensal penetration may contribute initiation relapse chronic inflammation.