DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Serrano‐Gómez, Diego; Leal, Juan; Corbí, Ángel L.

doi:10.1016/j.imbio.2005.05.011

Cited by 55 publications

(39 citation statements)

References 44 publications

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“…It was shown previously that pathogenic ascomycetes, including dermatophytes, bind to DCs via the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) (12,30). A novel pattern recognition pathway to detect dermatophytes via binding to DC-HIL (dendritic cell-associated heparan sulfate proteoglycan-integrin ligand) (31) and the subsequent phosphorylation of an ITAM (immunoreceptor tyrosine-based activation motif) was suggested previously (11).…”

Section: Discussionmentioning

confidence: 97%

The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells

et al. 2012

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ABSTRACTDermatophytes are the most common cause of superficial mycoses in humans and animals. They can coexist with their hosts for many years without causing significant symptoms but also cause highly inflammatory diseases. To identify mechanisms involved in the modulation of the host response during infection caused by the zoophilic dermatophyteArthroderma benhamiae, cell wall-associated surface proteins were studied. By two-dimensional gel electrophoresis, we found that a hydrophobin protein designated HypA was the dominant cell surface protein. HypA was also detected in the supernatant during the growth and conidiation of the fungus. TheA. benhamiaegenome harbors only a single hydrophobin gene, designatedhypA. AhypAdeletion mutant was generated, as was a complementedhypAmutant strain (hypAC). In contrast to the wild type and the complemented strain, thehypAdeletion mutant exhibited “easily wettable” mycelia and conidia, indicating the loss of surface hydrophobicity of both morphotypes. Compared with the wild type, thehypAdeletion mutant triggered an increased activation of human neutrophil granulocytes and dendritic cells, characterized by an increased release of the immune mediators interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha (TNF-α). For the first time, we observed the formation of neutrophil extracellular traps against dermatophytes, whose level of formation was increased by the ΔhypAmutant compared with the wild type. Furthermore, conidia of the ΔhypAstrain were killed more effectively by neutrophils. Our data suggest that the recognition ofA. benhamiaeby the cellular immune defense system is notably influenced by the presence of the surface rodlet layer formed by the hydrophobin HypA.

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Section: Discussionmentioning

confidence: 97%

The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells

et al. 2012

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“…Among these, DC-SIGN is a type II C-type lectin receptor expressed on immature dendritic cells that recognizes mannose and fructose carbohydrate moeties on diverse targets; DC-SIGN acts as a microbial pattern recognition receptor for multiple classes of microorganisms, in addition to several endogenous ligands, and can influence several cellular processes, including adhesion, phagocytosis, and regulation of the development of adaptive immunity (7). Of particular relevance to the present work, DC-SIGN can bind both Aspergillus (27,28) and the sialyl-Lewis-X antigen associated with neutrophil CD11b/CD18 complex (32,33). Whether the observed effect of DC-SIGN neutralization is related to its interaction with one or both of these ligands is a potential area for further investigation.…”

Section: Fig 6 Mechanism Of Neutrophil-mediated Maturation Of Myeloidmentioning

confidence: 93%

Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes

2012

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Invasive aspergillosis is a life-threatening complication of neutrophil deficiency or dysfunction. Neutropenia has previously been associated with enhanced influx of CD11b-expressing conventional dendritic cells to the lungs in response to Aspergillus species, but whether neutrophils directly modulate the function of dendritic cells in this infection is not known. We hypothesized that, in the setting of intrapulmonary challenge with Aspergillus, neutrophils promote the maturation and traffic of lung conventional dendritic cells to draining mediastinal lymph nodes. We report that neutropenia results in a marked accumulation of dendritic cells in the lungs of mice challenged with Aspergillus but greatly diminishes their egress to mediastinal lymph nodes independent of neutrophil microbicidal functions. Furthermore, the phenotype of lung dendritic cells was more immature in neutropenic animals than in nonneutropenic mice exposed to the microorganism. Consistent with this, coincubation with neutrophils greatly enhanced the upregulation of costimulatory molecules on dendritic cells exposed to Aspergillus in vitro, a process that was dependent on cell contact and the dendritic cell receptor DC-SIGN. Taken together, our data support an immunomodulatory cross talk between neutrophils and dendritic cells in the context of host response to Aspergillus that promotes the maturation and efflux of lung dendritic cells.

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“…Similar to TLRs (2), C-type lectins (CLs) are essential in recognizing pathogens and alerting the host to elicit immune responses against bacterial (3), fungal (4), and viral infections (5). Being structurally and functionally conserved (6), CLs bind to the sugar moieties of pathogen-associated molecular patterns (PAMPs) displayed on microbes (7), activate complements (8,9), promote phagocytosis (10), and induce cytokines (11).…”

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confidence: 99%

Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense

Zhang

Yang

Ang³

et al. 2010

The Journal of Immunology

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Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin–GPCR43 complex activates the NF-κB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin–GPCR43 complex. The collaboration among CRP–M-ficolin–GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membrane-associated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum-regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin–CRP provides a powerful template for future design of potential immunomodulators.

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DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Cited by 55 publications

References 44 publications

The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells

The Arthroderma benhamiae Hydrophobin HypA Mediates Hydrophobicity and Influences Recognition by Human Immune Effector Cells

Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes

Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense

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