Mannan-Binding Lectin Inhibits Candida albicans-Induced Cellular Responses in PMA-Activated THP-1 Cells through Toll-Like Receptor 2 and Toll-Like Receptor 4

Wang, Mingyong; Wang, Fanping; Jiao, Yang; Zhao, Di; Wang, Hongpo; Shao, Feng; Wang, Wenjun; Sun, Ruili; Ling, Mingzhi; Zhai, Jingjing; Song, Shanshan

doi:10.1371/journal.pone.0083517

Cited by 27 publications

(18 citation statements)

References 40 publications

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“…To further elucidate the actions of CMPs as TLR4 ligands in the HEK-TLR4 model we measured inflammatory gene transcripts that are typically produced in phagocytic cell lines stimulated with C . albicans [ 41 ] or mannose-based PAMPs [ 42 ]. Given the manufacturer’s recommended assay time course and reduced cell density requirements (0.5–1 x 10 5 cells/ml) for the reporter cell assays, initial cytokine ELISAs were unsuccessful.…”

Section: Resultsmentioning

confidence: 99%

Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14

et al. 2017

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The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene. TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40–50 μg/mL of CMP. Incubation on polymyxin B resin had no effect on CMP’s ligand activity, but neutralized LPS-spiked controls. HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα. Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes. Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses. SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B). These data confirm that engineered human cells expressing TLR4, MD2 and CD14 can respond to CMP with NF-κB activation and the response can be influenced by variations in CMP-mannosylation. Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.

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Section: Resultsmentioning

confidence: 99%

Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14

et al. 2017

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“…MBL by interaction with Toll-like receptor TLR-2 or TLR-4, inhibits C. albicans-induced interleukin (IL)-8 and tumor necrosis factora production from THP-1 cells. 17 The question is whether circulating MBL comes only from the liver and exerts an opsonization effect by eliminating fungal infection/colonization or whether MBL is also produced and released locally in the GI tract itself after fungal challenge. In the present study, we explored the expression of MBL in the gut epithelium and examined its impact on modulation of intestinal inflammation and C. albicans elimination.…”

Section: Introductionmentioning

confidence: 99%

Role of mannose-binding lectin in intestinal homeostasis and fungal elimination

et al. 2016

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Mannose-binding lectin (MBL) is a soluble lectin of the innate immune system that is produced by the liver and secreted into the circulation where it activates the lectin complement pathway, enhances phagocytosis of microorganisms by leukocytes, and modulates inflammation. MBL can recognize patterns on the surface of different pathogens, including Candida albicans. Our aims were to investigate whether MBL is expressed in the gut epithelium and to examine its effect on the modulation of intestinal inflammation and C. albicans elimination. Using reverse transcriptase-PCR, MBL transcripts were highly expressed in different parts of the mouse gut. MBL expression was also detected by immunoblotting and immunolocalization in response to C. albicans colonization of the gut; the highest expression of MBL was detected in the stomach. Blocking MBL by administering mannans to mice increased C. albicans colonization. MBL-deficient mice had a higher level of colonization than wild-type mice. Dextran sodium sulfate-induced colitis promoted C. albicans dissemination to the kidneys and lungs of MBL-deficient mice. MBL-deficient mice exhibited elevated expression of interleukin (IL)-17, IL-23, dectin-1, and Toll-like receptor-4. This study shows that MBL expression is induced in the gut in response to C. albicans sensing and is required for intestinal homeostasis and host defense against C. albicans.

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“…THP-1 cells differentiate into macrophages and express their particular ratios of different FcgR isotypes by PMA activation (20,21). The THP-1 cells used in the present study expressed FcgRI, FcgRII and FcgRIII, as shown by flow cytometry with mAbs against those individual receptors (Fig.…”

Section: Discussionmentioning

confidence: 64%

Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis

et al. 2015

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The Fc domain of human IgG1 binds to Fcc receptors (FccRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FccRIIA and FccRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH 2 CONH 2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FccRI and FccRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cellmediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FccR expression levels on the THP-1 cells was FccRII > FccRI > FccRIII and ADCP was inhibited by blocking antibodies against FccRI and FccRII. These results imply that the effect of the interchain disulfide bond cleavage on FccRs binding and ADCP is dependent on modifications of the cysteine residues and the FccR isotypes.

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Mannan-Binding Lectin Inhibits Candida albicans-Induced Cellular Responses in PMA-Activated THP-1 Cells through Toll-Like Receptor 2 and Toll-Like Receptor 4

Cited by 27 publications

References 40 publications

Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14

Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14

Role of mannose-binding lectin in intestinal homeostasis and fungal elimination

Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis

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