Document Detail

Innate immunity. A Spaetzle-like role for nerve growth factor β in vertebrate immunity to Staphylococcus aureus.
MedLine Citation:
PMID:  25359976     Owner:  NLM     Status:  In-Process    
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.
Lucy Hepburn; Tomasz K Prajsnar; Catherine Klapholz; Pablo Moreno; Catherine A Loynes; Nikolay V Ogryzko; Karen Brown; Mark Schiebler; Krisztina Hegyi; Robin Antrobus; Katherine L Hammond; John Connolly; Bernardo Ochoa; Clare Bryant; Michael Otto; Bas Surewaard; Suranjith L Seneviratne; Dorothy M Grogono; Julien Cachat; Tor Ny; Arthur Kaser; M Estée Török; Sharon J Peacock; Matthew Holden; Tom Blundell; Lihui Wang; Petros Ligoxygakis; Liliana Minichiello; C Geoff Woods; Simon J Foster; Stephen A Renshaw; R Andres Floto
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  346     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  641-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2014, American Association for the Advancement of Science.
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MeSH Terms
Grant Support
084953//Wellcome Trust; 089981//Wellcome Trust; G0700091//Medical Research Council; G0701932//Medical Research Council; //Department of Health

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