Researchers from MassGeneral Hospital for Children have identified a molecule that is key to how immune cells called macrophages recognize the bacteria E. coli. The study, which may lead to better ways of fighting infections, was issued March 24 as an advance online publication of the journal Nature.

The body's immune response against bacterial infection consists of the coordinated activities of a variety of white blood cells. Among these are 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 for MassGeneral Hospital for Children and head of the Laboratory of Developmental Immunology (left). "In this study, we look at a very ancient but very important process: how bacteria are recognized and eaten by immune cells like macrophages."

Ezekowitz's team — led primarily by postdoctoral fellow Mika Ramet, MD, PhD — identified 34 macrophage proteins essential to phagocytosis. The researchers found that inactivating one of these proteins called 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 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.

"PGRP-LC represents a new class of recognition molecules, and there are very similar genes in humans," Ezekowitz says. "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."