Hepburn, L;
Prajsnar, T.K.;
Klapholz, C;
Moreno, P;
Loynes, C;
Ogryzko, N.V.;
Brown, K;
... Floto, R. A.; + view all
(2014)
A Spaetzle-like role for Nerve Growth Factor β in vertebrate immunity to Staphylococcus aureus.
[Review].
Science
, 346
(6209)
pp. 641-646.
10.1126/science.1258705.
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Abstract
Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
| Type: | Article |
|---|---|
| Title: | A Spaetzle-like role for Nerve Growth Factor β in vertebrate immunity to Staphylococcus aureus |
| Identifier: | PMCID: 4255479 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/science.1258705 |
| Publisher version: | http://dx.doi.org/10.1126/science.1258705 |
| Language: | English |
| Additional information: | The published manuscript is available at Science via http://www.sciencemag.org/content/346/6209/641.full |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1473557 |
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