Downloads and Tools

•  Article PDF
  2.71 MB PDF document

This is an open access article.
Print this page Email this page

Recipient's Email:

---

Article Citation

RIS
MARC (XML)
FULL CITATION (TXT)

---

Share on Facebook

Authors: Rebecca L. Schmidt, Francesca M. Rinaldo, Shayla E. Hesse, Masakazu Hamada, Zachary Ortiz, Daniah T. Beleford, Andrea Page-McCaw, Jeffrey L. Platt and Amy H. Tang

Rebecca L. Schmidt

Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Francesca M. Rinaldo

Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Shayla E. Hesse

Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Masakazu Hamada

Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Zachary Ortiz

Department of Surgery, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Daniah T. Beleford

Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905

Andrea Page-McCaw

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 465 21st Avenue South, MRBIII, Room 4120B, Nashville, TN 37232-8240

Jeffrey L. Platt

Department of Surgery, Transplantation Biology, University of Michigan, Ann Arbor, MI 48109

Amy H. Tang

Corresponding author: TangAH@evms.edu
Department of Biochemistry and Molecular Biology and Department of Surgery Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Lewis Hall, Room 3148, Norfolk, Virginia 23507-1696

Abstract:
Drosophila responds to Gram-negative bacterial infection by activating the immune deficiency (IMD) pathway, leading to production of antimicrobial peptides (AMPs). As a receptor for the IMD pathway, peptidoglycan-recognition protein (PGRP), PGRP-LC is known to recognize and bind monomeric peptidoglycan (DAP-type PGN) through its PGRP ectodomain and in turn activate the IMD pathway. The questions remain how PGRP-LC is activated in response to pathogen infection to initiate the IMD signal transduction in Drosophila. Here we present evidence to show that proteases such as elastase and Mmp2 can also activate the IMD pathway but not the TOLL pathway. The elastase-dependent IMD activation requires the receptor PGRP-LC. Importantly, we find that live Salmonella/E.coli infection modulates PGRP-LC expression/receptor integrity and activates the IMD pathway while dead Salmonella/E.coli or protease-deficient E. coli do neither. Our results suggest an interesting possibility that Gram-negative pathogen infection may be partially monitored through the structural integrity of the receptor PGRP-LC via an infection-induced enzyme-based cleavage-mediated activation mechanism.

Received: August 25, 2011; Accepted: August 26, 2011

Preview: