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A team from the Institut Pasteur has recently shown that the tuberculosis bacillus hides from the immune system in its host's fat cells. This formidable pathogen is protected against even the most powerful antibiotics in these cells, in which it may remain dormant for years. This discovery, published in PLoS ONE, sheds new light on possible strategies for fighting tuberculosis. Attempts to eradicate the bacillus entirely from infected individuals should take these newly identified reservoir cells into account.
Mycobacterium tuberculosis, the bacillus responsible for tuberculosis can hide, in a dormant state, in adipose cells throughout the body. The bacterium is protected in this cellular environment, to which the natural immune defences have little access, and is inaccessible to isoniazid, one of the main antibiotics used to treat tuberculosis worldwide. These results were obtained by Olivier Neyrolles* and his colleagues from the Mycobacterial Genetics Unit directed by Brigitte Gicquel at the Institut Pasteur, in collaboration with Paul Fornès, a pathologist from Hôpital Européen Georges Pompidou. They raise questions of considerable importance in the fight against tuberculosis.
Tuberculosis kills almost two million people worldwide every year and is considered by the World Health Organisation to represent a global health emergency. However, the bacillus is much more prevalent in the world’s population than the statistics would lead us to believe, because only 5 to 10% of those infected actually develop tuberculosis. The bacillus may be present in a significant proportion of the population, remaining in a "dormant" state in the body, sometimes for years, and may be "reactivated" at any time. The risk of reactivation is particularly high in immunocompromised individuals, such as those infected with AIDS: the HIV virus and the tuberculosis bacillus make a formidable team, with each infectious agent facilitating the progression of the other.
Neyrolles’ team first demonstrated, in cell and tissue cultures, that adipose cells served as a reservoir for Mycobacterium tuberculosis, and that this protected the bacillus against isoniazid. They then investigated whether the pathogen was present in adipose cells in humans. They did this by testing for traces of the genetic structure of the bacillus in samples from people considered not to be infected. Analyses were carried out on samples from deceased subjects from Mexico, where tuberculosis is endemic, and from Parisian districts reporting very few cases of tuberculosis.
The bacterium was detected in the adipose tissue of about a quarter of these people, all of whom were unaware they were infected, in both Mexico and France. These results suggest that the bacillus responsible for tuberculosis can remain protected in the adipose tissue of the body in the absence of any sign of disease.
This work has important implications for the prevention of this disease. It helps to explain how, many years after first testing positive for tuberculosis, people with no trace of the microbe in the lungs may develop some form of tuberculosis attacking the lungs, bones or genitals. It also suggests that isoniazid treatment, prescribed to the close friends and family of patients as a preventative measure, may in some cases not provide sufficient protection against the disease. This is particularly important for immunocompromised patients and for people with AIDS, for whom a secondary infection with tuberculosis bacillus may have very serious consequences.
This work highlights the importance of the search for new targeted therapeutic weapons, such as new antibiotics, which must be able to reach the dormant bacillus that has been hiding in adipose cells without our knowing it.
* Olivier Neyrolles belongs to URA 2172, CNRS
« Is adipose tissue a place for Mycobacterium tuberculosis persistence?» PLoS One, 20 décembre 2006
Olivier Neyrolles (1,2), Rogelio Hernández-Pando (3) France Pietri-Rouxel (4), Paul Fornès (5), Ludovic Tailleux (1), Jorge Alberto Barrios Payán (3), Elisabeth Pivert (1), Yann Bordat (1), Diane Aguilar (3), Marie-Christine Prévost (6), Caroline Petit (4) & Brigitte Gicquel (1).
1. Unité de Génétique Mycobactérienne, Institut Pasteur, Paris
2. CNRS, URA 2172, Institut Pasteur, Paris
3. Département de Pathologie, Instituto Nacional de Ciencias Medicas y Nutricion, Tlaplan, Mexico
4. Département des Maladies Infectieuses, Institut Cochin, Paris
5. Département d’Anatomo-pathologie, Hôpital Européen Georges Pompidou, AP-HP, Paris
6. Laboratoire de Microscopie Electronique, Institut Pasteur, Paris
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