IU School of Medicine – Northwest Immunity Study Selected as Cover Story for Cell Host & Microbe

By: Indiana University Northwest Last Updated: August 23, 2010

Featured research looks at how immunity proteins protect mice from colitis iunlogo

The August issue of Cell Host & Microbe, a prestigious medical journal, features published research by IU School of Medicine – Northwest (IUSM-NW) scientists Roman Dziarski, Ph.D. and Dipika Gupta, Ph.D. The focus of their work looks at how immunity proteins provide protection to mice suffering from inflammatory bowel disease (IBD), also known as colitis.

The immunity proteins, referred to as peptidoglycan recognition proteins (PGRPs), found in the mice are also found in humans. These proteins, secreted by mucous membranes and skin, are potent bactericidal agents and constitute a first line of defense against bacterial infections.

Our research found PGRPs protect the host from colitis,” said IUSM-NW Professor of Microbiology and Immunology Roman Dziarski, Ph.D., who co-led the published study, titled, ‘Peptidoglycan Recognition Proteins Protect Mice from Experimental Colitis by Promoting Normal Gut Flora and Preventing Induction of Interferon-ɣ.’

Many people are affected by colitis and, unfortunately, we don’t know the cause,” Dziarski explained. “Studies suggest IBD affects one in 500 individuals. In order to try to help people with this disease, we first need to know what causes it and how it happens.”

Dziarski and Gupta have built upon more than 15 years of research to understand what causes colitis and how the PGRP genes play a role in protecting the body.

For their research, they used a mouse-model of colitis and worked with genetically engineered mice, which allowed them to remove each of the four PGRP genes, one at a time, to understand the functionality of each protein.

By inactivating each gene we were able to see what happened to the mouse if they didn’t have the immunity protein,” Dziarski said. “And as we expected, our research indicated that by inactivating the proteins, the mouse became much more sensitive to colitis. If they are more sensitive to colitis and don’t have the gene, then this means the gene protects the host from developing colitis.”

Co-researcher Dipika Gupta, Ph.D., Associate Professor of Biochemistry and Molecular Biology, noted the colitis symptoms in mice were very similar to what a human would experience with IBD.

Our research suggests these genes are needed to protect against colitis,” Gupta added. “Although we haven’t tested other mammals, we would assume the same would be true.”

The second part of the research focused on how the genes protect against colitis, which should provide them greater insight into the development of medicine to protect individuals who suffer from this disease.

Compounded research

The mouse-colitis study builds on earlier published research by both Dziarski and Gupta, which identified a role for the same proteins in another human disease, namely arthritis. This discovery was published in 2009 in the same medical journal, Cell Host & Microbe.

Dziarski and Gupta originally identified the four PGRP immunity proteins in groundbreaking research that was made possible by the mapping of the human genome. Subsequent to their original discovery, they identified PGRPs in zebrafish, which was published in 2007 in the highly-acclaimed medical journal, Immunity.

Dziarski explained that, in the zebrafish study, researchers learned not only that the colorful tropical freshwater fish possess the same four PGRPs as humans, but also that the zebrafish proteins actually are more active in killing bacteria than those found in humans.

Additional research

A future goal for Dziarski and Gupta is to enhance innate immunity in patients with impaired adaptive immune systems.

We believe these proteins could open up unexplored medical research,” Gupta said. “Future research on how to stimulate cells to over-produce these proteins, or ways to use them in the development of new drugs, may help in the treatment of patients with many diseases, including HIV/AIDs or those with compromised immune systems.”

Dr. Dziarski and Dr. Gupta’s collaborators include Dr. Sukumar Saha, Dr. Xuefang Jing, Dr. Shin Yong Park, Dr. Shiyong Wang, and Dr. Xinna Li.

The full research article published in Cell Host & Microbe is available online at www.cell.com/cell-host-microbe.