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Curr Biol. 2015 Jun 15;25(12):1606-12. doi: 10.1016/j.cub.2015.04.037. Epub 2015 May 28.

Draper/CED-1 mediates an ancient damage response to control inflammatory blood cell migration in vivo.

Author information

1
Department of Infection and Immunity and Bateson Centre, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. Electronic address: i.r.evans@sheffield.ac.uk.
2
School of Cellular and Molecular Medicine, Faculty of Medical Sciences, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
3
Department of Infection and Immunity and Bateson Centre, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
4
School of Cellular and Molecular Medicine, Faculty of Medical Sciences, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK. Electronic address: w.wood@bristol.ac.uk.

Abstract

Tissue damage leads to a robust and rapid inflammatory response whereby leukocytes are actively drawn toward the wound. Hydrogen peroxide (H2O2) has been shown to be an immediate damage signal essential for the recruitment of these inflammatory blood cells to wound sites in both Drosophila and vertebrates [1, 2]. Recent studies in zebrafish have shown that wound-induced H2O2 is detected by the redox-sensitive Src family kinase (SFK) Lyn within the responding blood cells [3]. Here, we show the same signaling occurs in Drosophila inflammatory cells in response to wound-induced H2O2 with mutants for the Lyn homolog Src42A displaying impaired inflammatory migration to wounds. We go on to show that activation of Src42A is necessary to trigger a signaling cascade within the inflammatory cells involving the ITAM domain-containing protein Draper-I (a member of the CED-1 family of apoptotic cell clearance receptors) and a downstream kinase, Shark, that is required for migration to wounds. The Src42A-Draper-Shark-mediated signaling axis is homologous to the well-established SFK-ITAM-Syk-signaling pathway used in vertebrate adaptive immune responses. Consequently, our results suggest that adaptive immunoreceptor-signaling pathways important in distinguishing self from non-self appear to have evolved from a more-ancient damage response. Furthermore, this changes the role of H2O2 from an inflammatory chemoattractant to an activator signal that primes immune cells to respond to damage cues via the activation of damage receptors such as Draper.

PMID:
26028435
PMCID:
PMC4503800
DOI:
10.1016/j.cub.2015.04.037
[Indexed for MEDLINE]
Free PMC Article

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