Internalization-dependent recognition of Mycobacterium avium ssp. paratuberculosis by intestinal epithelial cells

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease in ruminants.
• MAP's association with Crohn's disease highlights its importance in human and animal health.
• Understanding MAP's interaction with intestinal epithelial cells is crucial for disease pathogenesis.

Purpose of the Study:

• To investigate the interaction between MAP and differentiated intestinal epithelial cells.
• To elucidate the mechanisms of innate immune recognition and activation by MAP.

Main Methods:

• Studied MAP internalization and intracellular localization in epithelial cells.
• Assessed epithelial activation via chemokine secretion, measuring NF-kappaB and Erk pathways.
• Investigated the role of bacterial uptake using Rac-dependent inhibition.
• Identified pattern recognition receptors (TLR9, NOD1) and signaling adaptors (MyD88, RIP2) involved in MAP recognition.

Main Results:

• MAP was rapidly internalized and localized in late endosomes.
• MAP induced significant, internalization-dependent chemokine secretion via Erk signaling, independent of NF-kappaB.
• Inhibition of bacterial uptake abolished epithelial activation.
• Innate immune recognition involved intracellular TLR9 and NOD1, signaling through MyD88 and RIP2.

Conclusions:

• MAP internalization is essential for activating intestinal epithelial cells.
• This internalization-dependent immune activation pathway differs from extracellular bacterial stimulation.
• The findings provide insights into MAP pathogenesis and its potential role in inflammatory bowel diseases.