Dendritic cells sparked attention two years ago when researchers discovered that HIV enters them via a receptor called DC-SIGN. It is thought that the virus uses dendritic cells to hitch a lift directly to their target cells, T cells.

In the case of M. tuberculosis, it is already well established that the bacterium uses other receptors such as CR3 to infect macrophages. However, up to this point, interactions between dendritic cells and M. tuberculosis had remained a mystery.

"We started looking at DC-SIGN as a potential target because we knew that M. tuberculosis is processed differently in dendritic cells and macrophages," said Olivier Neyrolles, who directed the research at the Pasteur Institute in Paris. "Moreover," he added, "DC-SIGN binds to mannose, and the mycobacterial cell wall is unique among bacteria in having a high mannose content."

The researchers confirmed that DC-SIGN binds to ManLam, a component of the bacterial cell wall particularly rich in mannose. The researchers also found that DC-SIGN was just as effective at capturing other strains of mycobacteria, such as M. bovis. Their research is published today in the Journal of Experimental Medicine.

What's more, unlike most macrophages, alveolar macrophages - the primary target of M. tuberculosis in vivo, appear to express DC-SIGN, the researchers report. "It wouldn’t surprise me if M. tuberculosis also takes advantage of DC-SIGN to infect alveolar macrophages" Neyrolles suggested. The researchers are currently investigating the possibility.

The second group to discover the DC-SIGN-TB link is based at the Vrij Universiteit Medical Center in Amsterdam. The Dutch researchers showed that upon binding to DC-SIGN, ManLam deactivates dendritic cells, causing a reduction in the body's ability to clear the infection, which can be reversed by administering antibodies that block DC-SIGN.

This finding suggests "the tantalizing possibility that by blocking DC-SIGN it will be possible to inhibit both HIV transmission and immunosuppression by M. tuberculosis," said Teunis Geijtenbeek, lead researcher on the Dutch team. Those results are published alongside the French research.

This work is "clearly an important milestone," said Stefan Kaufmann, an expert in disease immunology based at the Max-Planck Institute in Berlin, Germany. Kaufmann hopes that the new insights into the interaction between M. tuberculosis and the immune system will unravel why only some infected individuals develop disease symptoms and not others. However, he notes, it is necessary to first test the theory in animal models.

Kaufmann is also optimistic that the research could provide a new strategy for developing a vaccine against TB. Because the available BCG vaccine fails to protect adults against pulmonary tuberculosis, the most prevalent form of the disease, he said, "we urgently need a new vaccine against tuberculosis."

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HIV-1, TEM. CDC/Dr. Edwin P. Ewing, Jr. Right: Mycobacterium tuberculosis SEM. Tuberculosis Research Section, NIAID, NIH.