The role of pattern recognition receptors in the innate recognition of<i>Candida albicans</i>

Zheng, Nanxin; Wang, Yan; Hu, Dandan; Yan, Lan; Jiang, Yuanying

doi:10.1080/21505594.2015.1014270

Cited by 45 publications

(27 citation statements)

References 203 publications

(284 reference statements)

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“…Mucosal epithelial cells express a variety of fungal pattern recognition receptors (PRRs) to initiate and orchestrate immune responses (4, 5), but the exact composition of the receptors employed by enteric epithelial cells to recognize C. albicans is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

Klaile

Schäfer

et al. 2017

mBio

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Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA) knockdown abolished CXCL8 (interleukin-8) secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion.

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Section: Introductionmentioning

confidence: 99%

Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

Klaile

Schäfer

et al. 2017

mBio

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“…albicans ) can target a disparate array of PRRs on the surface of human professional phagocytes [ 24 , 25 ]. Toll-like receptors and C-type lectin receptors together with other fungal-relevant receptors, including FcγR, CR3, CD36, SCARF1 [ 26 ] and lactosylceramide (LacCer) [ 27 – 31 ] sense simultaneously several C . albicans pathogen associated molecular patterns (PAMPs) to orchestrate the so-called “PRRs crosstalk”.…”

Section: Introductionmentioning

confidence: 99%

Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses

et al. 2015

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Several pathogens have been described to enter host cells via cholesterol-enriched membrane lipid raft microdomains. We found that disruption of lipid rafts by the cholesterol-extracting agent methyl-β-cyclodextrin or by the cholesterol-binding antifungal drug Amphotericin B strongly impairs the uptake of the fungal pathogen Candida albicans by human monocytes, suggesting a role of raft microdomains in the phagocytosis of the fungus. Time lapse confocal imaging indicated that Dectin-1, the C-type lectin receptor that recognizes Candida albicans cell wall-associated β-glucan, is recruited to lipid rafts upon Candida albicans uptake by monocytes, supporting the notion that lipid rafts act as an entry platform. Interestingly disruption of lipid raft integrity and interference with fungus uptake do not alter cytokine production by monocytes in response to Candida albicans but drastically dampen fungus specific T cell response. In conclusion, these data suggest that monocyte lipid rafts play a crucial role in the innate and adaptive immune responses to Candida albicans in humans and highlight a new and unexpected immunomodulatory function of the antifungal drug Amphotericin B.

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“…In phagocytes, activation of host responses is achieved through recognition of fungal cell wall structures by immune cell surface receptors on blastoconidia; the signal delivered intracellularly initiates a cascade of events leading to activation and nuclear translocation of NF-B, production of cytokines, recruitment of polymorphonuclear leukocytes, and release of reactive oxygen species. NLRP3 inflammasome activation holds also a central role in anti-Candida host defense as it is involved in processing of pro-interleukin-1␤ (pro-IL-1␤) and IL-1␤ secretion, leading to the priming of an inflammatory response (11)(12)(13). We hypothesized that subinhibitory concentrations of micafungin (MFG) may alter biofilm formation, enhancing the antifungal efficacy of immune cells and, indirectly, modulating immune responses to the benefit of host defenses in the containment of Candida biofilms.…”

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confidence: 99%

Pharmacodynamic and Immunomodulatory Effects of Micafungin on Host Responses against Biofilms of Candida parapsilosis in Comparison to Those of Candida albicans

Simitsopoulou

Chlichlia

Kyrpitzi

et al. 2018

Antimicrob Agents Chemother

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Micafungin (MFG) demonstrates potent activity against biofilms of and, the most frequent opportunistic fungal pathogens. Little is known about its immunopharmacologic effect on antibiofilm activity of phagocytic cells following exposure to biofilms. In this study, we investigated the effects of MFG on human neutrophil-mediated damage of and biofilms by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] and the potential mechanisms underlying the immunomodulatory MFG activities on cultured monocyte-derived THP-1 cells in response to these biofilms by reverse transcription-PCR and sandwich and multiplex enzyme-linked immunosorbent assay. Preexposure of to subinhibitory MFG concentrations significantly enhanced neutrophil-mediated biofilm damage, an effect that appears to be species specific since a comparable effect was not observed with drug-pretreated biofilms. Human THP-1 cells responded to both biofilms through Toll-like receptor 2 (TLR2) and TLR4 upregulation, modest TLR6 involvement, and enhanced NLRP3 activation, whereas the signal was relayed to the nucleus via NF-κB p65 activation. MFG caused 2- to 3-fold lower TLR2 and TLR4 mRNA levels than those caused by either organism. biofilms induced a robust proinflammatory response, whereas biofilms either alone or in the presence of MFG caused increased interleukin-1β (IL-1β) production, but small amounts of IL-8, IL-23, and tumor necrosis factor alpha. In conclusion, MFG may condition THP-1 cells toward an inflammatory response through TLR2/TLR4 recruitment. Inflammatory signals observed with biofilms are considerably reduced upon exposure of THP-1 cells to biofilms, possibly enhancing fungal survival and increasing biofilm pathogenicity.

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The role of pattern recognition receptors in the innate recognition ofCandida albicans

Cited by 45 publications

References 203 publications

Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses

Pharmacodynamic and Immunomodulatory Effects of Micafungin on Host Responses against Biofilms of Candida parapsilosis in Comparison to Those of Candida albicans

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