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A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
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2014 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 346, no 6209, 641-646 p.Article in journal (Refereed) Published
Abstract [en]

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 NLRP4 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.

Place, publisher, year, edition, pages
2014. Vol. 346, no 6209, 641-646 p.
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Other Basic Medicine
Identifiers
URN: urn:nbn:se:umu:diva-96463DOI: 10.1126/science.1258705ISI: 000343799700052PubMedID: 25359976OAI: oai:DiVA.org:umu-96463DiVA: diva2:765041
Funder
Wellcome trust, 084953Wellcome trust, 089981
Available from: 2014-11-21 Created: 2014-11-21 Last updated: 2017-12-05Bibliographically approved

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Ny, Tor

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