A Spaetzle-like role for nerve growth factor β in vertebrate immunity to Staphylococcus aureus

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Science  31 Oct 2014:
Vol. 346, Issue 6209, pp. 641-646
DOI: 10.1126/science.1258705

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Overcoming staph infections is hardwired

Several evolutionarily conserved components of antistaphylococcal immunity have been identified, using Drosophila as a model organism. However, no vertebrate ortholog has been identified for the Toll ligand Spaetzle, which plays a key role in controlling gram-positive infection in flies. Hepburn et al. have now identified NGF-β as a functional equivalent to Spaetzle in vertebrates. NGF-β acts as a paracrine “alarmin” orchestrating macrophage and neutrophil responses to S. aureus infection. People with deleterious mutations in genes encoding NGF-β or its high-affinity receptor TRKA are predisposed to recurrent and severe staph infections. S. aureus proteins selectively trigger macrophage production of NGF-β, which enhances uptake and superoxide-dependent killing of S. aureus, stimulates proinflammatory cytokine production, and promotes neutrophil recruitment. Moreover, TrkA silencing in vivo increases susceptibility to S. aureus. Thus, the NGF-β–TRKA pathway is a critical, evolutionarily conserved component of vertebrate immunity to S. aureus infection.

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