Intestinal epithelial CD98 directly modulates the innate host response to enteric bacterial pathogens

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• CD98 (Carboxypeptidase E) is a type II transmembrane glycoprotein.
• CD98 expression is elevated in intestinal epithelial cells (IECs) during inflammation.
• Enteropathogenic Escherichia coli (EPEC) causes intestinal inflammation by injecting effector proteins into IECs.

Purpose of the Study:

• To investigate the interaction between CD98 and EPEC.
• To examine the role of CD98 in intestinal infection models.
• To elucidate the function of CD98's extracellular loop in host-pathogen interactions.

Main Methods:

• In vitro studies using Caco2-BBE cells with CD98 knockdown via siRNA.
• Ex vivo analysis of intestinal tissues.
• In vivo studies using FVB wild-type (WT) and villin-CD98 transgenic mice infected with Citrobacter rodentium.
• Surface Plasmon Resonance (SPR) to detect direct binding between CD98 and bacterial proteins.

Main Results:

• CD98 overexpression in mouse colons increased C. rodentium attachment and pro-inflammatory markers.
• Proliferative markers (Ki-67, cyclin D1) were elevated in infected hCD98 Tg mice.
• CD98 knockdown reduced EPEC adherence to Caco2 cells.
• SPR confirmed direct binding between recombinant CD98 and bacterial proteins, particularly involving CD98's extracellular loop.

Conclusions:

• CD98's extracellular loop plays a critical role in binding to EPEC and C. rodentium.
• CD98 overexpression exacerbates intestinal inflammation and bacterial attachment.
• CD98 is important in the innate host defense against attaching and effacing (A/E) pathogens.