Nature Immunology pp 769 - 776

The immune system has to recognize potential threats from microbes and react quickly and specifically. Researchers have now shown human immune cells integrate multiple signals obtained by 'tasting' their microbial invader through sensors known as Toll-like receptors (TLRs), according to the August issue of Nature Immunology. By using combinations of different TLRs, including those on the cell surface and internal receptors within specialized compartments where engulfed bacteria or viruses reside, these human dendritic cells alert the rest of the immune system to even tiny amounts of pathogen.

Dendritic cells are known to play a key role in immunity by presenting antigens to prime specific immune responses as well as secreting molecules, known as cytokines, that signal 'danger'. Lanzavecchia and colleagues show activation of multiple TLRs results in amplified signals and lead to higher production of the cytokines known as interleukins 12 and 23. This action recruits more immune cells to the infected area and arms them against perceived intracellular threats. Such responses are critical for pathogens like the tuberculosis bacteria or viruses. This type of immune response, since it directs immune cells to seek out and kill infected cells, needs to be tightly controlled. The use of multiple signals, akin to dual keys, affords the immune system both the sensitivity and specificity required for such reactions.

Nature Immunology pp 844 - 851

Stimulation of nicotinic acetylcholine receptors (nAChRs), which are found on both nerves and immune cells, can initiate a program that shuts down the inflammatory machinery of immune cells, according to a paper in the August issue of Nature Immunology. Such a trigger can be exploited to prevent inflammation. This new work adds to accumulating evidence that suggests the nervous system is intimately linked to the immune system.

Macrophages are immune cells that produce large amounts of proteins and chemicals to produce inflammatory effects. Wouter de Jonge and colleagues find that triggering nAChRs on macrophages sets off certain small molecules known as Jak2 and STAT3 in the cells to reduce inflammation by decreasing the production of offending proteins. To demonstrate the usefulness of this finding, they stimulate a major nerve (the vagus nerve) that links the brain to the gut in a mouse experiment that imitates inflammation after intestinal surgery. Normally, intestinal surgery can induce severe inflammation that leads to a condition known as postoperative ileus, which causes patients to suffer pain, nausea and vomiting. However, stimulation of the nerve, which specifically works through nAChR and STAT3, prevents inflammation of the intestine after surgery. Hence, therapies aimed at tickling nerves might provide new clinical avenues to treat postoperative ileus and other inflammatory conditions.