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Synopsis PLOS Medicine published a Synopsis with every Research Article until May 2006. An Editors' Summary aimed at all medical professionals, whatever their specialty, and the general public, is now published at the end of each Research Article.

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DC-SIGN and Lung Pathogenesis in Patients with Tuberculosis

  • Published: November 15, 2005
  • DOI: 10.1371/journal.pmed.0020410

C-type lectins are carbohydrate-binding cell surface molecules with a wide range of biological functions, many of which are related to immunity. Despite its name, dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is not only expressed on dendritic cells but also on specialized macrophages in the placenta and lung. A number of pathogens are known to interact with DC-SIGN, and some (including HIV) seem to have evolved to derive advantages from these interactions.

Recent in vitro studies have shown that DC-SIGN can interact with Mycobacterium tuberculosis through a lipoglycan (a molecule composed of sugars and fatty acids) on the mycobacterial envelope called lipoarabinomannan (LAM). Trying to understand the role of DC-SIGN in tuberculosis (TB), Ludovic Tailleux and colleagues have focused on the interaction between M. tuberculosis and DC-SIGN–expressing cells in the lungs of human patients.

The researchers studied a total of 74 individuals, including 40 with TB, 11 with sarcoidosis, 14 with asthma, and nine control participants without active lung infection or inflammation. All patients underwent bronchoalveolar lavage (BAL), a procedure that yields cells and proteins from the lower respiratory tract. The researchers then examined BAL cell populations after staining for various cell-surface markers by flow cytometry, and found that, in individuals without TB, very few alveolar macrophages (an average of 3%) expressed DC-SIGN. In contrast, an average of 30% (and up to 70%) of macrophages from patients with TB expressed the lectin.

Tailleux and colleagues then incubated alveolar macrophages from a patient without TB ex vivo with M. tuberculosis, which resulted in infection of a subset of the cells. When the researchers examined DC-SIGN expression, they found that both infected and noninfected (bystander) cells in the population started to express DC-SIGN. The effect on bystander cells suggests that soluble factors from the microbe and/or the infected cells can induce DC-SIGN expression. Further functional ex vivo studies with cells from human patients indicated that DC-SIGN expression renders alveolar macrophages more susceptible to infection.

The authors propose a scenario where complement receptors mediate most of the initial infection of alveolar macrophages in a naïve host, and where—once the infection is established—DC-SIGN–expressing alveolar macrophages become preferential target cells for M. tuberculosis. Future work will be focused on identifying the soluble factors involved, and on determining whether DC-SIGN induction is an essential part of TB pathogenesis.