Bordetella, the pathogen underlying whooping cough, short-circuits the host immune response by triggering the antiinflammatory cytokine IL-10. Now, Nagamatsu and colleagues nab the bacterial protein that does the job.
Bacteria often thwart inflammatory responses by injecting effector proteins into host cells through a syringe-like organelle called the type III secretion system (T3SS). These effector proteins manipulate the host immune response in a variety of ways. Here, Nagamatsu et al. discover the first bacterial effector protein known to trigger IL-10.
Bordetella secretes at least two T3SS effector proteins into host cells, BopC and BopN. BopC induces cell death, and BopN is now shown to trigger IL-10 when it moves into the nucleus of dendritic cells and macrophages. BopN inhibited MAP kinase signaling and activated the transcription factor SP-1, which is known to promote IL-10 production. BopN also induced NF-κB p50 translocation at the expense of p65, a situation that may also promote IL-10 production.
Mice infected with a BopN-deficient strain of Bordetella produced less IL-10, effectively recruited neutrophils to the site of infection, and rid themselves of the bug. Mice lacking IL-10 cleared infection whether or not BopN was intact. And exposing mice to the BopN-deficient strain protected them against later challenge with wild-type bacteria, perhaps by ramping up the production of the inflammatory cytokine IFN-γ.
Because MAP kinase and NF-κB signaling control the expression of thousands of genes, BopN might alter other cytokines as well. A prior study showed that an unidentified Bordetella T3SS protein shuts down IFN-γ production. Whether this was a result of IL-10 suppressing IFN-γ–producing cells, of BopN altering NF-κB activation, or the action of a different effector protein altogether remains to be seen.