Study Identifies Key Immune System Molecule


BOSTON (ASRN.ORG)- Researchers at MassGeneral Hospital for Children have identified a molecule that is key to how white blood cells called macrophages recognize the common bacteria E. coli. The study may lead to better ways of fighting infections.

The body's immune response against baterial infection consists of the coordinated activities of a variety of white blood cells. Among these are cells known as macrophages, which ingest and destroy the invaders in a process called phagocytosis. In the current study, researchers from the Laboratory of Developmental Immunology, studied macrophages from the fruitfly Drosophila.

"The basic templates of how organisms protect themselves against infection go back millions of years in evolution, so we can learn lessons from flies that apply to humans," says R. Alan Ezekowitz, MBChB, DPhil, chief of Pediatrics and head of the Laboratory of Developmental Immunology. "In this study we look at a very ancient but very important process: how bacteria are recognized and eaten by immune cells called phagocytes [a group that includes macrophages]." 

Using a new method of turning off specific genes, Ezekowitz's team led primarily by postdoctoral fellow Mika Ramet, MD, PhD, identified 34 macrophage proteins that are essential to the process of phagocytosis. One of these proteins is a cell surface receptor -- a molecule that sits on a cell’s outer membrane and receives chemical signals -- called PGRP-LC. The researchers found that inactivating PGRP-LC destroyed macrophages' ability to recognize and ingest E. coli bacteria but not another type of bacteria called S. aureus, suggesting that the protein is critical to the macrophage's specific response against what are called gram-negative bacteria. To confirm this association, postdoctoral fellow Pascal Mantruelli, PhD, created a group of Drosophila with a mutated version of PGRP-LC and found the flies were much more susceptible to E. coli infection than were normal fruitflies. 

"PGRP-LC represents a new class of recognition molecules, and there are very similar genes in humans," Ezekowitz says. "The next question to ask is whether this protein plays a related role in humans. Understanding the role these proteins play could eventually lead to new ways of fighting infection and to helping us figure out why some people are more susceptible to specific infections."

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