Cellular safety shelters allow TB agent to survive in infected individuals

Imagine that you are a bad guy running from the law, and the sheriff is about to catch up to you. If you want, you can be Butch Cassidy or the Sundance Kid or any other charismatic bad guy. Or maybe you're a wizard in Harry Potter and Dementors are about to catch up to you.

But then, just as the sheriff, or the Dementor, or whatever, catches up, you wave a magic wand and instead of killing or capturing you, your nemesis transforms into a big tent inside of which you can hide. And the tent is made out of food that you can eat.

This, metaphorically (and thus not exactly accurate, but close enough) is what Mycobacterium tuberculosis (Mtb) does. This strategy, only now just discovered, is the explanation for the mystery of tuberculosis infection: TB is capable of hiding, while in remission, in a patient's body indefinitely. It is now believed, according to a study release five minutes ago in the journal PLoS Pathogens, that Mtb cells utilize a piece of their own cell surface to induce killer immune cells -- macrophages -- to convert into foamy fat storing cells, inside of which the Mtb hides and, according to this research, remain alive.

There are a lot of details still to work out, and this research has only been done so far in vitro (which, by the way, is one of the advantages of this specific research ... see paper for details), but this research constitutes a major step forward.

The paper is available on line at PLoS Pathogens. Here is the Author's Summary:

Mycobacterium tuberculosis, the causative agent of tuber- culosis, is responsible for dramatic health problems globally. It is estimated that this pathogen infects one- third of the human population and causes three million deaths annually. Most individuals remain asymptomatic for several years before developing an active disease. In such individuals, the bacilli are not cleared but rather persist in a dormant state. Major goals of TB research are to (i) understand how the bacilli remain alive for years within infected individuals, and (ii) find how to prevent their reactivation and hence clinical disease. During dormancy, most of the bacilli are confined to granulomas that consist of well-defined aggregates of different host immune cells. Granulomas prevent spreading of bacilli. In this study, we analyzed the role of a particular cell population foundwithin granulomas, the ''foamy macrophages''. These cellsare filled with droplets of lipids, a well-known nutrient forpersistent bacilli. We found that within these cells, thebacilli do not replicate, but remain alive and seem tointernalize host lipids. The foamy macrophages might thusconstitute a reservoir for persisting bacilli within theirhuman host, and could provide a relevant model forscreening of new antimicrobials against non-replicatingpersistent mycobacteria.

Peyron P, Vaubourgeix J, Poquet Y, Levillain F, Botanch C, et al. (2008) Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence. PLoS Pathog 4(11): e1000204. doi:10.1371/journal.ppat.1000204