2 April 2015
Dr Si Ming Man, recipient of the 2015 NHMRC/RG Menzies Fellowship, is the first author of some ground-breaking research on deadly infectious diseases, published recently in leading scientific journal Nature Immunology.
In fact the research, which focuses on the highly virulent and often fatal infectious bacterium, Francisella tularensis, is receiving significant attention worldwide.
The research findings were generated by Dr Man and his colleagues at the St. Jude Children's Research Hospital in Memphis, Tennessee.
The hospital’s scientists have discovered major ‘switches’ that activate the immune system to kill the bacterium, potentially leading to protective drugs and vaccines.
Dr Man, who is a postdoctoral fellow in St Jude’s Department of Immunology and was responsible for designing many of the experiments in the paper and analysing the results, described the findings this way:
‘Infectious diseases are a leading cause of death in the world. Francisella tularensis is a very infectious bacterium which kills more than 30 per cent of infected individuals, if left untreated. The bacterium is transmitted by air, insect bites, or consumption of contaminated food or water. Infection occurs when the bacterium invades and hides inside a type of immune cells known as macrophages.
‘In our new study, we identified an intricate network of immune proteins that seek to destroy the bacterium. Our work has shown that once the bacterium gets inside a macrophage, a receptor in the cell called cGAS recognizes bacterial DNA to activate the cell by producing signalling molecules known as type I interferons. Type I interferons enable the cell to “switch on” a crucial gene-activating factor known as IRF1. IRF1 activates a “killer’s instinct” in the cell and allow the cell to produce immune proteins to fight the infection.
‘Further experiments identified these immune proteins to be “guanylate-binding proteins”, which literally attack and kill the bacteria. Dying bacteria release more of their DNA and a second receptor that detects DNA is activated in the cell to trigger another wave of attack and inflammatory response, which eventually clear the infection.
‘Our work for the first time identified a remarkable relationship between immune proteins and show that they work together to fight and control a deadly pathogen. Therapies that target and enhance the functions of these immune proteins could help us win battles against deadly infectious diseases.’
Image description: Francisella bacteria (labelled in green) infect and replicate in macrophages, a type of immune cells that helps fight against infections. Macrophages produce defense proteins called guanylate-binding proteins or GBPs (labelled in red) to attack the invading bacteria. The control centre of a macrophage containing DNA, which encodes genetic information of the cell, is labelled in blue.
The full article can be access here: www.nature.com/ni/journal/vaop/ncurrent/full/ni.3118.html