Cutting Edge: <i>Candida albicans</i> Hyphae Formation Triggers Activation of the Nlrp3 Inflammasome

Joly, Sophie; Ma, Ning; Sadler, Jeffrey J.; Soll, David R.; Cassel, Suzanne L.; Sutterwala, Fayyaz S.

doi:10.4049/jimmunol.0901323

Cited by 276 publications

(301 citation statements)

References 20 publications

Supporting

Mentioning

284

Contrasting

Unclassified

Order By: Relevance

“…However, accumulating evidence indicates that infection with many pathogens including bacteria, viruses and fungi induces the proinflammatory cell death of infected macrophages through the activation of caspase-1 [5][6][7][8][9][10][11][12][13][14][15][16][17]. The Nod-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) is critical for caspase-1 activation and the secretion of IL-1b and IL-18 in response to multiple microbial molecules and endogenous danger molecules, whereas the NLR family, CARD domain containing 4 (NLRC4) protein is believed to sense bacterial flagellin and induce caspase-1 activation [18,19].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages

et al. 2010

View full text Add to dashboard Cite

Aeromonas hydrophila is a Gram-negative pathogen that causes serious infectious disease in humans. A. hydrophila induces apoptosis in infected macrophages, but the host proinflammatory responses triggered by macrophage death are largely unknown. Here, we demonstrate that the infection of mouse macrophages with A. hydrophila triggers the activation of caspase-1 and release of IL-1b. Caspase-1 activation was abrogated in macrophages deficient in Nod-like receptor family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), but not NLR family, CARD domain containing 4 (NLRC4). The activation of the NLRP3 inflammasome was mediated by three cytotoxins (aerolysin, hemolysin and multifunctional repeat-in-toxin) produced by A. hydrophila. Our results indicated that the NLRP3 inflammasome senses A. hydrophila infection through the action of bacterial cytotoxins.Key words: Aeromonas . Caspase-1 . Nod-like receptor Supporting Information available online IntroductionThe genus Aeromonas is responsible for a significant number of animal and human infections. Aeromonas are opportunistic human pathogens that can cause intestinal and extraintestinal, wound, soft tissue, skin, and blood infections and septicemia. The most common human disease associated with Aeromonas infection is gastroenteritis with diarrhea symptoms. Among the 21 species that have been differentiated based on DNA-DNA hybridization, A. caviae, A. veronii biotype sobria and A. hydrophila are most commonly associated with human infections and account for more than 85% of all clinical isolates [1,2].Recently, it has been reported that infection with A. hydrophila induces apoptosis in macrophages [3,4]. Although the cytotoxicity by the bacteria is believed to enable the bacteria to evade eradication and clearance by the macrophages, the host proinflammatory responses triggered by the death of the macrophages remain unknown.Induction of apoptosis is considered a virulence mechanism of pathogenic bacteria that can cause tissue damage and Here, we investigated the cell death of macrophages infected with A. hydrophila and demonstrate that the bacteria cause pyroptosis with caspase-1 activation via the NLRP3 inflammasome. Aerolysin, hemolysin (HlyA) and multifunctional repeat-intoxin (RtxA) produced by A. hydrophila are required to elicit the NLRP3 inflammasome and necrotic cell death. We identify the essential bacterial and host factors for eliciting caspase-1 activation and proinflammatory responses. SHORT COMMUNICATION Results and discussionInfection with A. hydrophila induces caspase-1 activation, IL-1b release and pyroptosis It has been reported that aerolysin produced by A. salmonicida induces caspase-1 activation in CHO cells [20,21]. However, whether whole bacterial infection by A. hydrophila leads to caspase-1 activation in macrophages has not been elucidated. We examined caspase-1 activation in infected primary mouse BMderived macrophages (BMM) and observed that BMM infected with WT strai...

show abstract

Section: Introductionmentioning

confidence: 99%

Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Moreover, filament formation is essential for the activation of the inflammasome and the subsequent IL-1b release [18]. Therefore, we investigated whether hyphae formation was required for, or otherwise influenced, IFN-b induction.…”

Section: Identification Of Yeast Components Capable Of Inducing Ifn-bmentioning

confidence: 99%

Recognition of yeast nucleic acids triggers a host‐protective type I interferon response

et al. 2011

View full text Add to dashboard Cite

Although type I interferons (IFN-a/b) have been traditionally associated with antiviral responses, their importance in host defense against bacterial pathogens is being increasingly appreciated. Little is known, however, about the occurrence and functional role of IFN-a/b production in response to pathogenic yeasts. Here, we found that conventional DCs, but not macrophages nor plasmacytoid DCs, mounted IFN-b responses after in vitro stimulation with Candida spp. or Saccharomyces cerevisiae. These responses absolutely required MyD88, a Toll-like receptor (TLR) adaptor molecule, and were partially dependent on TLR9 and TLR7. Moreover, Candida DNA, as well as RNA, could recapitulate the IFN-b response. After intravenous challenge with Candida albicans, most mice lacking the IFN-a/b receptor died from their inability to control fungal growth, whereas all WT controls survived. These data suggest that recognition of yeast nucleic acids by TLR7 and TLR9 triggers a host-protective IFN-a/b response.Key words: Candida albicans . Cytokines . DCs . Fungal infections . Macrophages Supporting Information available online IntroductionCandida albicans (C. albicans) is, among fungi, the most common pathogen of humans. Although they are normally harmless commensals of the intestinal and urinary tract, C. albicans and other Candida species can cause recurrent mucosal infections in otherwise healthy subjects and life-threatening conditions in hospitalized or immunocompromised patients [1]. In recent years, C. albicans has become the fourth most common cause of bloodstream infections, with an incidence of between 1 and 24 cases per 100 000 and a mortality rate of 30-50% [2]. Since the host immune status is the major factor that determines the transition of C. albicans from commensalism to pathogenicity, elucidating the mechanisms underlying immune response initiation, particularly those underlying recognition of fungal components, is crucial to developing new and more effective strategies to combat these infections. In fact, despite the availability of new classes of antifungal drugs, current available therapies are only partially effective and are associated with significant side effects.Antimicrobial responses are initiated by the activation of germ-line-encoded receptors (pattern-recognition receptors, PRRs) expressed by cells of the innate immune system, mainly by macrophages and DCs, which monitor potential portals of pathogen entry. Each PRR binds directly or indirectly to one or more evolutionary conserved microbial molecules (pathogenassociated molecular patterns, PAMPs) and triggers intracellular signal transduction cascades culminating in distinctive transcriptional and nontranscriptional responses. By this mechanism, PRRs link microbial recognition with the selective activation of specific arms of the innate immune system [3].Ã These authors have contributed equally to this study. Eur. J. Immunol. 2011. 41: 1969-1979 DOI 10.1002 Immunity to infection 1969Considerable progress has been recently made in the identification ...

show abstract

“…Several members of the NLR family, including NLRP3 (also known as NALP3 and cryopyrin), form large multiprotein complexes, termed inflammasome, which in turn activate caspase-1, leading to the processing and secretion of IL-1β and IL-18 (Bryant and Fitzgerald, 2009). Recent reports link IL-1β production induced by C. albicans to the NLRP3 inflammasome (Gross et al, 2009;Hise et al, 2009;Joly et al, 2009;Kumar et al, 2009;van de Veerdonk et al, 2009a). Noteworthy, TLR2, Dectin-1, and NLRP3 were crucial for the protection from dissemination of C. albicans in a murine model of oral mucosal infection (Hise et al, 2009).…”

Section: Nod-like Receptorsmentioning

confidence: 99%

Epithelial Cells and Innate Antifungal Defense

2010

View full text Add to dashboard Cite

The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. Clinical observations indicate that mucocutaneous Candida infections are commonly associated with defective cell-mediated immune responses. The importance of the innate immune system as a first-line defense against pathogenic challenge has long been recognized. Over the last decade, many key molecules mediating innate host defense have been identified. Central to these developments is the discovery of pattern recognition receptors such as Toll-like receptors and C-type lectin-receptors that induce innate immune responses and also modulate cellular and humoral adaptive immunity during Candida infections. Although a large amount of information is now available in systemic infections, little is known about localized infections. We address the most relevant pattern recognition receptors and their signaling mechanisms in oral epithelial cells, to gain a better understanding of their contributions to antifungal innate immunity.

show abstract

Cutting Edge: Candida albicans Hyphae Formation Triggers Activation of the Nlrp3 Inflammasome

Cited by 276 publications

References 20 publications

Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages

Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages

Recognition of yeast nucleic acids triggers a host‐protective type I interferon response

Epithelial Cells and Innate Antifungal Defense

Contact Info

Product

Resources

About