Dataset Information

Epidermal hepcidin is required for neutrophil response to bacterial infection.

ABSTRACT: Novel approaches for adjunctive therapy are urgently needed for complicated infections and patients with compromised immunity. Necrotizing fasciitis (NF) is a destructive skin and soft tissue infection. Despite treatment with systemic antibiotics and radical debridement of necrotic tissue, lethality remains high. The key iron regulatory hormone hepcidin was originally identified as a cationic antimicrobial peptide (AMP), but its putative expression and role in the skin, a major site of AMP production, have never been investigated. We report here that hepcidin production is induced in the skin of patients with group A Streptococcus (GAS) NF. In a GAS-induced NF model, mice lacking hepcidin in keratinocytes failed to restrict systemic spread of infection from an initial tissue focus. Unexpectedly, this effect was due to its ability to promote production of the CXCL1 chemokine by keratinocytes, resulting in neutrophil recruitment. Unlike CXCL1, hepcidin is resistant to degradation by major GAS proteases and could therefore serve as a reservoir to maintain steady-state levels of CXCL1 in infected tissue. Finally, injection of synthetic hepcidin at the site of infection can limit or completely prevent systemic spread of GAS infection, suggesting that hepcidin agonists could have a therapeutic role in NF.

SUBMITTER: Malerba M

PROVIDER: S-EPMC6934188 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Epidermal hepcidin is required for neutrophil response to bacterial infection.

Malerba Mariangela M Louis Sabine S Cuvellier Sylvain S Shambat Srikanth Mairpady SM Hua Camille C Gomart Camille C Fouet Agnès A Ortonne Nicolas N Decousser Jean-Winoc JW Zinkernagel Annelies S AS Mathieu Jacques Rr JR Peyssonnaux Carole C

The Journal of clinical investigation 20200101 1

Novel approaches for adjunctive therapy are urgently needed for complicated infections and patients with compromised immunity. Necrotizing fasciitis (NF) is a destructive skin and soft tissue infection. Despite treatment with systemic antibiotics and radical debridement of necrotic tissue, lethality remains high. The key iron regulatory hormone hepcidin was originally identified as a cationic antimicrobial peptide (AMP), but its putative expression and role in the skin, a major site of AMP produ ...[more]

PMID: 31600168

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Project description:In the absence of adaptive immunity displayed by animals, plants respond locally to biotic challenge via inducible basal defense networks activated through recognition and response toconserved pathogen associated molecular patterns (PAMPs). In addition, immunity can be induced in tissues remote from infection sites via systemic acquired resistance (SAR), initiated following gene-for-gene recognition between plant resistance proteins and microbial effectors.The nature of the mobile signal and remotely activated networks responsible for establishing SAR remain unclear. Here we show that despite the absence of PAMP contact, systemically responding leaves rapidly activate a SAR transcriptional signature with strong similarity to local basal defense. Jasmonates have previously been implicated in systemic signalling in response to wounding and plant herbivory but not SAR. We present several lines of evidence that suggest jasmonates may also be central to SAR. Jasmonic acid (JA) rapidly accumulates in phloem exudates of leaves challenged with an avirulent strain of Pseudomonas syringae. In systemically responding leaves transcripts associated with jasmonate biosynthesis are upregulated and JA increases transiently. SAR can be mimicked by foliar JA application and is abrogated in mutants impaired in jasmonate synthesis or response. We conclude that, jasmonate signalling appears to mediate long-distance information transmission. Moreover, the systemic transcriptional response shares extraordinary overlap with local herbivory and wounding responses, indicating that jasmonates may be central to an evolutionarily conserved signalling network, which decodes multiple abiotic and biotic stress signals. Experimenter name: William Truman Experimenter phone: +44 (0)1392 263789 Experimenter fax: +44 (0)1392 263434 Experimenter address: School of Biosciences Experimenter address: Geoffrey Pope Building Experimenter address: Stocker Road Experimenter address: Exeter Experimenter address: Devon Experimenter zip/postal_code: EX4 4QD Experimenter country: UK Keywords: infection

Dataset Information

Epidermal hepcidin is required for neutrophil response to bacterial infection.

Publications

Epidermal hepcidin is required for neutrophil response to bacterial infection.

Similar Datasets

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