<i>Malassezia</i> yeasts activate the <scp>NLRP</scp>3 inflammasome in antigen‐presenting cells via <scp>S</scp>yk‐kinase signalling

Kistowska, Magdalena; Fenini, Gabriele; Janković, Dragana; Feldmeyer, Laurence; Kerl, Katrin; Bosshard, Philipp P.; Contassot, Emmanuel; French, Lars E.

doi:10.1111/exd.12552

Cited by 75 publications

(81 citation statements)

References 60 publications

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“…and C . albicans recognized by C-type lectin receptors transduce signals to induce NLRP3 inflammasome activation in macrophages and DCs [19, 20, 23]. M .…”

Section: Discussionmentioning

confidence: 99%

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Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum

et al. 2017

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Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H. capsulatum triggers caspase-1 activation and IL-1β production through NLRP3 inflammasome. By reciprocal blocking of Dectin-1 or Dectin-2 in single receptor-deficient DCs and cells from Clec4n-/-, Clec7a-/-, and Clec7a-/-Clec4n-/- mice, we discovered that while Dectin-2 operates as a primary receptor, Dectin-1 serves as a secondary one for NLRP3 inflammasome. In addition, both receptors trigger Syk-JNK signal pathway to activate signal 1 (pro-IL-1β synthesis) and signal 2 (activation of caspase-1). Results of pulmonary infection with H. capsulatum showed that CD103+ DCs are one of the major producers of IL-1β and Dectin-2 and Dectin-1 double deficiency abolishes their IL-1β response to the fungus. While K+ efflux and cathepsin B (but not ROS) function as signal 2, viable but not heat-killed H. capsulatum triggers profound lysosomal rupture leading to cathepsin B release. Interestingly, cathepsin B release is regulated by ERK/JNK downstream of Dectin-2 and Dectin-1. Our study demonstrates for the first time the unique roles of Dectin-2 and Dectin-1 in triggering Syk-JNK to activate signal 1 and 2 for H. capsulatum-induced NLRP3 inflammasome activation.

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“…and C . albicans recognized by C-type lectin receptors transduce signals to induce NLRP3 inflammasome activation in macrophages and DCs [19, 20, 23]. M .…”

Section: Discussionmentioning

confidence: 99%

“…Malassezia spp. triggers IL-1β production in human monocyte-derived DCs through Dectin-1 [19]. TLR-2 and Dectin-1 are both involved in induction of pro-IL-1β transcription by hyphal forms of C .…”

Section: Discussionmentioning

confidence: 99%

Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum

et al. 2017

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“…These include PAMPs such as LPS, fungal zymosan, bacterial toxins, and also the bacteria Listeria monocytogenes (Meixenberger et al, 2010), S. aureus (Munoz-Planillo et al, 2009), and Propionibacterium acnes (Kistowska et al, 2014b; Qin et al, 2014), as well as yeasts like Candida albicans (Hise et al, 2009) and of the Malassezia spp. (Kistowska et al, 2014a). NLRP3 can also be activated by danger-associated molecules that are not derived from pathogens but often associated with cellular stress, the so-called DAMPs, including extracellular ATP (Mariathasan et al, 2006), asbestos (Dostert et al, 2008), amyloid-β (Halle et al, 2008), DNA:RNA hybrids (Kailasan Vanaja et al, 2014), and crystals such as gout-causing monosodium urate (MSU) (Martinon et al, 2006), silica (Dostert et al, 2008), or cholesterol (Duewell et al, 2010).…”

Section: The Inflammasomesmentioning

confidence: 99%

“…The etiological agent of pityriasis versicolor, Malassezia was shown to activate the NLRP3 inflammasome via the dectin-1 and Syk signaling cascade, causing the release of IL-1β (Kistowska et al, 2014a). To date, no IL-1 blocker has been evaluated for the treatment of Malassezia- associated skin diseases.…”

Section: Skin Diseases With Il-1 Involvementmentioning

confidence: 99%

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

2017

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In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra) Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.

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“…Kistowska et al showed that different species of Malassezia present the potential to activate the NLRP3 inflammasome in antigen-presenting cells, leading to a high synthesis of IL-1β. 107 …”

Section: Dermatological Diseases Associated With Inflammasomesmentioning

confidence: 99%

Inflammasomes and dermatology

Sá

Neto

2016

An. Bras. Dermatol.

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Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.

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Malassezia yeasts activate the NLRP3 inflammasome in antigen‐presenting cells via Syk‐kinase signalling

Cited by 75 publications

References 60 publications

Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum

Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

Inflammasomes and dermatology

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