A mycobacterium that causes skin ulcers protects itself from the immune system by suppressing dendritic cell (DC) activity, according Coutanceau et al. (page 1395).
In the initial stages of Mycobacterium ulcerans infection, the skin puckers up into nodules that brim with bacteria and inflammatory cells. But this primary immune response gradually loses steam. As disease progresses, the inflammatory cells disappear and the nodules transform into festering ulcers. The bug seems to enforce immune suppression even outside the lesions as patients with ulcers have poor systemic cellular responses.
Coutanceau et al. found several structural similarities between mycolactone—a lipid toxin produced by the bug—and known immune-suppressive drugs, and postulated that the toxin might function as an immune modulator. They now find that mycolactone hinders the DCs that drive T cell activation. The toxin prevented skin-derived DCs from migrating to the draining lymph nodes and blood-derived DCs from acquiring their usual antigen-presenting and chemokine-secreting functions. But why the toxin initially allows the primary immune response to occur and how it hobbles DCs after ulcers form are still unclear.
Other mycobacteria, such as the bug that causes tuberculosis, secrete related biologically active lipids. Some of them target macrophages and inhibit the production of inflammatory cytokines, not chemokines. The team is now investigating the structural and molecular basis of this difference in toxin function.