How does Mycobacterium tuberculosis infect the lung?

November 14, 2005

Tuberculosis (TB) is the most common major infectious disease today. It is estimated that two billion people--or one-third of the world's population--are chronically infected without active symptoms. Nine million new cases of active disease are diagnosed annually, resulting in two million deaths. TB is predominantly a lung disease. It is caused by a microbe called Mycobacterium tuberculosis which infects lung cells, but it is still not clear how exactly this happens. Ludovic Tailleux, Olivier Neyrolles, and colleagues (from the Pasteur Institute, in collaboration with the Necker and Saint-Louis Hospitals, in Paris) have found that a molecule called DC-SIGN plays a crucial part.

The researchers wanted to examine whether lung cells from patients with TB were different from those of healthy people or those with different lung diseases, and what that tells us about the way the infection spreads in the lung. In particular, they looked at the surface of the lung cells, because this is the part directly involved in the first contact with the Mycobacterium. As they report now in the international open-access medical journal PLoS Medicine, they studied 74 individuals, 40 of whom had TB, 25 had other inflammatory lung diseases, and 9 had neither active TB nor lung inflammation and served as healthy "controls." The patients underwent a procedure called broncho-alveolar lavage that washes out some of the secretions and cells from the lower respiratory tract. The researchers then analyzed the cells in different ways. They concentrated on a type of cell called a macrophage (the natural target of Mycobacterium) and found that macrophages from patients with TB had much more the DC-SIGN protein on their surface than macrophages from patients with other diseases or from the control individuals.

They then took macrophages from a control individual (which had very low levels of DC-SIGN) and infected them with Mycobaterium under laboratory conditions. They found that shortly after infection not only the infected cells but also some of their neighbours started to display DC-SIGN on their surface. They also found that having DC-SIGN on the surface made uninfected cells much more susceptible to infection.

These results suggest that DC-SIGN has an important function in amplifying TB infection in the lung. Interfering with DC-SIGN function might therefore be a new way to fight TB, a disease that is becoming increasingly resistant to existing therapies and for which new drugs are urgently needed.
-end-
Citation: Tailleux L, Pham-Thi N, Bergeron-Lafaurie A, Herrmann JL, Charles P, et al. (2005) DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis. PLoS Med 2(12): e381.

CONTACT:
Olivier Neyrolles
Institut Pasteur
28 Rue du Dr Roux
Paris, France 75015
+00-33-1-45-68-88-40
+00-33-1-45-68-88-43 (fax)
neyrolle@pasteur.fr

PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS MEDICINE (www.plosmedicine.org) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.

All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere--to read, download, redistribute, include in databases, and otherwise use--subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.


PLOS

Related Tuberculosis Articles from Brightsurf:

Scientists find new way to kill tuberculosis
Scientists have discovered a new way of killing the bacteria that cause tuberculosis (TB), using a toxin produced by the germ itself.

Blocking the iron transport could stop tuberculosis
The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply.

Tuberculosis: New insights into the pathogen
Researchers at the University of W├╝rzburg and the Spanish Cancer Research Centre have gained new insights into the pathogen that causes tuberculosis.

Unmasking the hidden burden of tuberculosis in Mozambique
The real burden of tuberculosis is probably higher than estimated, according to a study on samples from autopsies performed in a Mozambican hospital.

HIV/tuberculosis co-infection: Tunneling towards better diagnosis
1.2 million people in the world are co-infected by the bacteria which causes tuberculosis and AIDS.

Reducing the burden of tuberculosis treatment
A research team led by MIT has developed a device that can lodge in the stomach and deliver antibiotics to treat tuberculosis, which they hope will make it easier to cure more patients and reduce health care costs.

Tuberculosis: Commandeering a bacterial 'suicide' mechanism
The bacteria responsible for tuberculosis can be killed by a toxin they produce unless it is neutralized by an antidote protein.

A copper bullet for tuberculosis
Tuberculosis is a sneaky disease, and the number one cause of death from infectious disease worldwide.

How damaging immune cells develop during tuberculosis
Insights into how harmful white blood cells form during tuberculosis infection point to novel targets for pharmacological interventions, according to a study published in the open-access journal PLOS Pathogens by Valentina Guerrini and Maria Laura Gennaro of Rutgers New Jersey Medical School, and colleagues.

How many people die from tuberculosis every year?
The estimates for global tuberculosis deaths by the World Health Organisation (WHO) and the Institute for Health Metrics and Evaluation (IHME) differ considerably for a dozen countries, according to a study led by ISGlobal.

Read More: Tuberculosis News and Tuberculosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.