Research ArticleExperimental Studies
Open Access

Dectin-1/SYK Activation Induces Antimicrobial Peptide and Negative Regulator of NF-κB Signaling in Human Oral Epithelial Cells

MEGUMI INOMATA, MASAYO ABE, YASUKO KAWASE, TORU HAYASHI, SHIGERU AMANO and HIROSHI SAKAGAMI
In Vivo May 2024, 38 (3) 1042-1048; DOI: https://doi.org/10.21873/invivo.13537

Abstract

Background/Aim: Oral epithelial cells serve as the primary defense against microbial exposure in the oral cavity, including the fungus Candida albicans. Dectin-1 is crucial for recognition of β-glucan in fungi. However, expression and function of Dectin-1 in oral epithelial cells remain unclear. Materials and Methods: We assessed Dectin-1 expression in Ca9-22 (gingiva), HSC-2 (mouth), HSC-3 (tongue), and HSC-4 (tongue) human oral epithelial cells using flow cytometry and real-time polymerase chain reaction. Cell treated with β-glucan-rich zymosan were evaluated using real-time polymerase chain reaction. Phosphorylation of spleen-associated tyrosine kinase (SYK) was analyzed by western blotting. Results: Dectin-1 was expressed in all four cell types, with high expression in Ca9-22 and HSC-2. In Ca9-22 cells, exposure to β-glucan-rich zymosan did not alter the mRNA expression of chemokines nor of interleukin (IL)6, IL8, IL1β, IL17A, and IL17F. Zymosan induced the expression of antimicrobial peptides β-defensin-1 and LL-37, but not S100 calcium-binding protein A8 (S100A8) and S100A9. Furthermore, the expression of cylindromatosis (CYLD), a negative regulator of nuclear factor kappa B (NF-κB) signaling, was induced. In HSC-2 cells, zymosan induced the expression of IL17A. The expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a negative regulator of NF-κB signaling, was also induced. Expression of other cytokines and antimicrobial peptides remained unchanged. Zymosan induced phosphorylation of SYK in Ca9-22 cells, as well as NF-κB. Conclusion: Oral epithelial cells express Dectin-1 and recognize β-glucan, which activates SYK and induces the expression of antimicrobial peptides and negative regulators of NF-κB, potentially maintaining oral homeostasis.

Key Words:

Oral epithelial cells serve as the frontline defense barrier against pathogenic microorganisms, playing a crucial role in preventing infection onset (1). These epithelial cells respond to pathogenic microorganisms by releasing antimicrobial peptides, chemokines, and cytokines (1). The induction of these molecules is initiated by the recognition of pathogen-associated molecular patterns through pattern recognition receptors (1, 2). These encompass various types of receptors, such as toll-like receptors (TLRs) and C-type lectin receptors (3). Specifically, TLR4 acts a receptor for lipopolysaccharide and plays a pivotal role in periodontitis development and progression (4).

The oral cavity hosts diverse microflora, with Candida albicans as the most abundant fungal species (5, 6). Fungal cell walls contain β-glucan (7). C-Type lectin domain-containing 7A, known as Dectin-1, is a C-type lectin receptor encoded by the CLEC7A gene and is involved in β-glucan recognition (8, 9). This recognition activates Dectin-1 through the spleen-associated tyrosine kinase (SYK)/caspase recruitment domain-containing protein 9 (CARD9) pathway via an immunoreceptor tyrosine-based activation motif-like motif. This motif is present in the intracellular signaling tail of Dectin-1 and plays a role in recruiting SYK, an event that results in the dimerization of Dectin-1 (10). SYK activates the CARD9–B-cell lymphoma 10–mucosa-associated lymphoid tissue lymphoma translocation protein 1 complex inducing canonical nuclear factor kappa B (NF-κB) activation through the phosphorylation of phospholipase Cγ2 and subsequent activation of protein kinase C. This pathway induces the production of cytokines and chemokines, such as interleukin (IL)-6, IL-23, IL-1β, IL-12, and tumor necrosis factor (TNF) (10-13). The cytokines induce T-helper (Th) 17 response (11-13) and IL-17 production from immune cells other than Th17 cells, such as epithelial, innate lymphoid, and γδ T-cells (14-17). The Th17 response contributes to antifungal immunity (13). In addition, Dectin-1 activation has been linked to enhanced phagocytosis and the generation of antimicrobial peptide production, and reactive oxygen species to combat bacterial infections (18, 19). Notably, deficiency of Dectin-1-mediated immunity in humans and mice leads to susceptibility to C. albicans, emphasizing the vital role in defense against fungal infection (20-22). Dectin-1 likely contributes to the regulation of oral immune homeostasis. Nevertheless, it remains unclear whether oral epithelial cells express Dectin-1 and what the consequences are of its activation through the Dectin-1/SYK pathway on these cells. This study sought to assess the impact of Dectin-1 activation via the Dectin-1–SYK pathway, with a specific focus on epithelial cells.

Materials and Methods

Cell culture. Gingival Ca9-22 cells, mouth HSC-2 cells, and HSC-3 and HSC-4 tongue cells (Riken Cell Bank, Tsukuba, Japan) were cultured at 37°C in Dulbecco’s modified Eagle’s medium supplemented with 10% heat-inactivated (56°C for 30 min) fetal bovine serum, as described elsewhere (23).

Flow cytometry. Flow cytometry was performed, as described previously (24). Briefly, the HSC-2, HSC-3, HSC-4, and Ca9-22 cells (1×106 cells/well) were treated with either 10 μg/ml zymosan purchased from Merck (Darmstadt, Germany) or 5 μg/ml ultrapure lipopolysaccharide (LPS) from Porphyromonas gingivalis purchased from Invivogen (San Diego, CA, USA) for 6 h, then were fixed with 4% formaldehyde and permeabilized with methanol. Then the cells were stained with rabbit monoclonal antibody to human Dectin-1 (60128; Cell Signaling Technology, Danvers, MA, USA) for 1 h and were incubated with Alexa488-conjugated anti-rabbit IgG antibody (Thermo Fisher Scientific, Waltham, MA, USA) for 1 h. Dectin-1 expression was analyzed with an SH800 cell sorter (Sony, Minato, Tokyo, Japan). Data shown are representative of three experiments.

Western blotting. Ca9-22 cells seeded in six-well plates (1×106 cells/well) were treated with 10 μg/ml zymosan for 30 or 60 min, washed with phosphate-buffered saline, and lysed with 300 μl lysis buffer (25) at 4°C for 15 min. The collected lysates were centrifuged, and the supernatants were boiled with sodium dodecyl sulphate sample buffer for 5 min and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (4-20% gradient gel) under reducing conditions. The separated proteins were transferred onto a polyvinylidene difluoride membrane (Trans-Blot Turbo Mini PVDF Transfer Pack; Bio-Rad Laboratories, Hercules, CA, USA) using a Trans-Blot Turbo transfer device (Bio-Rad Laboratories; constant 25 V for 5 min). The membranes were blocked with blocking buffer (Toyobo, Osaka, Japan) for 1 h. Immunoreactive bands were detected using phosphorylation-specific rabbit polyclonal antibodies against SYK (2710), AKT serine/threonine kinase 1 (AKT) (Thr308) (4056) and NF-κB p65 (3033), and rabbit polyclonal antibody against AKT (4691) obtained from Cell Signaling Technology; mouse monoclonal antibodies against SYK (sc-1240) and rabbit polyclonal antibody against tubulin (PM054) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA) or MBL (Tokyo, Japan). ECL Prime western blotting detection reagent (Thermo Fisher Scientific) and the ChemiDoc XRS Plus system (Bio-Rad Laboratories) were used for visualization. Western blotting was used for qualitative assay. Data shown are representative of three experiments.

RNA isolation and quantitative reverse transcription-polymerase chain reaction. Total RNA was extracted from cells using NucleoSpin RNA (TaKaRa Bio, Kusatsu, Japan). Total RNA (500 ng) was reverse transcribed using ReverTraAce reverse transcriptase (Toyobo) with oligo21dT and random hexamer primers. Quantitative reverse transcription-polymerase chain reaction was performed using a LightCycler 480 (Roche Diagnostics, Basel, Switzerland). The predesigned primer sets for IL6, IL8, IL1β, IL17A, IL17F, cathelicidin antimicrobial peptide (CAMP), cylindromatosis (CYLD), defensin beta 1 (DEFB1), S100 calcium-binding protein A8 (S100A8), S100A9, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) were obtained from TaKaRa Bio. The primer sequences are not shown, as the primers were provided by the manufacturer. The reaction conditions were as follows: pre-denaturation at 95°C for 30 s, denaturation at 95°C for 5 s, and annealing at 60°C for 20 s, for 40 cycles. Gene-expression levels were assessed using the ∆∆Ct method. Results are shown as the relative expression levels of the genes of interest normalized to that of β-actin. Mean±standard deviation values for one (triplicate) of the three independent experiments are shown.

Statistical analysis. Data are shown as the mean±standard deviation. p-Values were calculated using Student’s t-test. Differences with p<0.05 were considered significant.

Results

Dectin-1 expression in Ca9-22, HSC-2, HSC-3, and HSC-4 human oral epithelial cells. In previous work, we confirmed Dectin-1 expression in human periodontal ligament fibroblasts and human gingival fibroblasts using flow cytometry (24). Here, we extended our analysis to human oral epithelial cells, Ca9-22, HSC-2, HSC-3, and HSC-4. Our findings reveal that Dectin-1 was expressed in all these oral epithelial cells (Figure 1A). Notably, HSC-2 cells exhibited the highest expression of Dectin-1, followed by Ca9-22, as determined by real-time polymerase chain reaction (Figure 1B). Conversely, HSC-4 cells displayed the lowest Dectin-1 expression among these cells (Figure 1B). Collectively, these results demonstrate the presence of Dectin-1 in human oral epithelial cells to varying expression levels.

Figure 1.
Figure 1.

Expression of Dectin-1 in Ca9-22, HSC-2, HSC-3 and HSC-4 human oral epithelial cells. (A) Cell surface expression of Dectin-1 was quantified via flow cytometry. Red, stained with Dectin-1 antibody; green, stained with control antibody; blue, unstained. Data shown are representative of three experiments. (B) RNA was extracted, and quantitative reverse transcription-polymerase chain reaction was used to determine the levels of Dectin-1 gene (CLEC7A). Mean±standard deviation (SD) values for one (triplicate) of the three independent experiments are shown.

Expression of chemokines, cytokines, antimicrobial peptides, and negative regulators of NF-κB signaling in response to β-glucan-rich zymosan. We examined the responsiveness of Ca9-22 and HSC-2 cells to β-glucan as these exhibited higher levels of Dectin-1 expression than HSC-3 and HSC-4 cells.

In Ca9-22 cells, there was no detectable expression of IL6, IL8, and IL17A under baseline conditions (Figure 2A and Table I). A previous report suggested that the stimulation of oral epithelial cells with various TLR ligands does not trigger the production of inflammatory cytokines and chemokines, including IL6 and IL8 (26). Consistent with this, exposure to ultrapure P. gingivalis LPS, a TLR4 ligand, failed to induce the expression of IL6, IL8, and IL17A in Ca9-22 cells (Figure 2A). Similarly, β-glucan-rich zymosan did not induce the expression of these cytokines (Figure 2A). Although IL1β and IL17F were expressed under basal conditions, they were not significantly induced by either LPS or zymosan (Figure 2A).

Figure 2.
Figure 2.

Effects of β-glucan-rich zymosan on the gene expression of cytokines, chemokines, and antimicrobial peptides in Ca9-22 cells. Ca9-22 cells were treated with either 10 μg/ml zymosan or 5 μg/ml Porphyromonas gingivalis lipopolysaccharide (LPS) for 6 h. RNA was extracted, and quantitative reverse transcription-polymerase chain reaction was used to determine the levels of interleukin (IL)6, IL8, IL1β, IL17A, IL17B (A), defensin beta 1 (DEFB1), cathelicidin antimicrobial peptide (CAMP), S100 calcium-binding protein A8 (S100A8), S100A9 (B), cylindromatosis (CYLD), and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) (C) in treated cells relative to the corresponding levels in the untreated cells. Mean±standard deviation values for one (triplicate) of the three independent experiments are shown. *Significantly different at p<0.05 versus untreated cells by Student’s t-test. n.d.: Not detected.

View this table:
Table I.

Expression of cytokines, chemokines, antimicrobial peptides, and negative regulators of nuclear factor kappa B (NF-κB) signaling in Ca9-22, HSC-2, periodontal ligament fibroblasts (PDLFs), and gingival fibroblasts (GFs) after treatment with zymosan for 1 h (relative to the untreated control).

In Ca9-22 cells, constitutive expression of genes for antimicrobial peptides β-defensin-1 (DEFB1), LL-37 (CAMP) and S100A9 was observed under control conditions (Figure 2B). Notably, zymosan stimulation resulted in the up-regulation of DEFB1 and CAMP (Figure 2B). LPS did not significantly induce the expression of these peptides (Figure 2B). In contrast, there was no detectable basal expression of S100A8, encoding another antimicrobial peptide, and this remained unchanged following stimulation with zymosan or LPS (Figure 2B). Furthermore, zymosan induced the expression of CYLD, which negatively regulates NF-κB signaling by deubiquitylation (27) (Figure 2C). Conversely, the expression of TNFAIP3, another factor involved in regulating NF-κB signaling (28), remained unaltered (Figure 2C). LPS did not induce the expression of negative regulators of NF-κB signaling (Figure 2C).

HSC-2 cells exhibited baseline expression of IL6, IL8, IL1β, IL17A, and IL17F (Figure 3A and Table I). Notably, zymosan and LPS induced the expression of IL17A (Figure 3A). HSC-2 cells baseline expression of DEFB1, S100A8 and S100A9 (Figure 3B). However, zymosan and LPS failed to induce the expression of these molecules (Figure 3B). HSC-2 cells lacked expression of DEFB1, and this remained unchanged following stimulation by β-glucan or LPS (Figure 3B). Interestingly, TNFAIP3, but not CYLD, was induced in HSC-2 cells by both stimulators (Figure 3C).

Figure 3.
Figure 3.

Effects of β-glucan-rich zymosan on the expression of cytokines, chemokines and antimicrobial peptides in HSC-2 cells. HSC-2 cells were treated with either 10 μg/ml zymosan or 5 μg/ml Porphyromonas gingivalis lipopolysaccharide (LPS) for 6 h. RNA was extracted, and quantitative reverse transcription-polymerase chain reaction was used to determine the levels of interleukin (IL)6, IL8, IL1β, IL17A, IL17B (A), defensin beta 1 (DEFB1), cathelicidin antimicrobial peptide (CAMP), S100 calcium-binding protein A8 (S100A8), S100A9 (B), cylindromatosis (CYLD), and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) (C) in treated cells relative to the corresponding levels in the untreated cells. Mean±standard deviation values for one (triplicate) of the three independent experiments are shown. *Significantly different at p<0.05 versus untreated cells by Student’s t-test. n.d.: Not detected.

Dectin-1/SYK-mediated recognition of β-glucan-rich zymosan in Ca9-22 cells. Phosphorylation of SYK, which is recruited to immunoreceptor signaling motifs upon activation, was observed in Ca9-22 cells treated with zymosan (Figure 4). Moreover, critical downstream pathways, such as AKT and NF-κB p65, were also activated (Figure 4). These findings strongly suggest that β-glucan-rich zymosan induces immune responses in Ca9-22 cells through downstream signaling mediated by Dectin-1/SYK.

Figure 4.
Figure 4.

Dectin-1/spleen-associated tyrosine kinase (SYK) signaling pathway is involved in cell activation induced by β-glucan-rich zymosan in Ca9-22 cells. Ca9-22 cells were treated with 10 μg/ml zymosan for up to min. Cell lysates were immunoblotted using antibodies for SYK, phosphorylated SYK (pSYK), AKT serine/threonine kinase 1 (AKT), pAKT(Thr308), phosphorylated nuclear factor kappa B (pNF-κB), and tubulin. Data shown are representative of three experiments.

Discussion

Similar to the intestinal tract, the oral cavity harbors a diverse microbiota. While Dectin-1 expression and its roles have been reported in intestinal epithelial cells (29, 30), such information was lacking in oral epithelial cells. Hence, as far as we are aware, this study marks the first investigation into Dectin-1 expression and its responsiveness in various oral epithelial cells.

Prior research has indicated that oral epithelial cells typically do not produce cytokines or chemokines in response to various TLR ligands (26). Similarly, in line with the findings regarding TLR ligands, this study demonstrates that Dectin-1 ligand does not trigger the expression of inflammatory cytokines or chemokines (Figure 2A). Instead, interestingly, this study shows that Dectin-1 ligand induces the expression of antimicrobial peptides, including DEFB1 and CAMP (Figure 2B) and negative regulator of NF-κB signaling, such as CYLD and TNFAIP3 (Figure 2C). To date, Dectin-1/SYK activation has not been shown to induce antimicrobial peptide and negative regulator of NF-κB signaling in human oral epithelial cells. These findings suggest that oral epithelial cells, functioning as a physical barrier, are intricately regulated to maintain homeostasis, avoiding excessive inflammatory response to microbial stimuli.

In our prior research, we confirmed the presence of Dectin-1 expression in periodontal ligament fibroblasts and gingival fibroblasts (Table I) (24). Notably, these fibroblasts induced the production of cytokines and chemokines in response to Dectin-1 ligand (24). Furthermore, these fibroblasts responded to P. gingivalis LPS and generated cytokines (24). These findings suggest that the fibroblasts trigger the inflammatory responses when epithelial cells fail to defend against pathogens, which leads to maintenance of oral homeostasis.

Dectin-1-mediated production of antimicrobial peptides has been linked to shifts in gut bacterial composition, potentially worsening conditions like dextran sulfate sodium salt-induced enteritis and ovalbumin-induced airway inflammation (29). In the oral cavity, responses involving Dectin-1-mediated antimicrobial peptide production might contribute to homeostasis, but sustained production possibly induces the onset of oral diseases, such as oral candidiasis and periodontal disease, resulting from dysbiosis.

Conclusion

Oral epithelial cells express Dectin-1 and recognize β-glucan, which activates SYK and induces the expression of antimicrobial peptides and negative regulators of NF-κB signaling, which are potentially involved in maintaining oral homeostasis and prevention of the onset of oral diseases, such as oral candidiasis and periodontal disease.

Acknowledgements

The Authors would like to thank Editage for editing and reviewing this article for English language.

Footnotes

  • Authors’ Contributions

    Conceptualization: Megumi Inomata, Hiroshi Sakagami. Methodology: Megumi Inomata, Shigeru Amano, Toru Hayashi. Validation: Megumi Inomata. Formal analysis: Megumi Inomata, Toru Hayashi. Investigation: Megumi Inomata, Masayo Abe, Yasuko Kawase, Toru Hayashi, Hiroshi Sakagami. Resources: Megumi Inomata, Shigeru Amano, Hiroshi Sakagami. Writing – original draft preparation: Megumi Inomata. Writing – review and editing: Shigeru Amano, Masayo Abe, Toru Hayashi, Hiroshi Sakagami. Visualization: Megumi Inomata, Shigeru Amano, Toru Hayashi, Hiroshi Sakagami. Supervision: Shigeru Amano, Hiroshi Sakagami. Project administration: Megumi Inomata, Shigeru Amano, Hiroshi Sakagami. Funding acquisition: Megumi Inomata, Hiroshi Sakagami.

  • Funding

    This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science to M.I. (21K09849).

  • Conflicts of Interest

    The Authors declare there are no competing interests.

  • Received December 19, 2023.
  • Revision received February 3, 2024.
  • Accepted February 8, 2024.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Groeger S,
    2. Meyle J
    : Oral mucosal epithelial cells. Front Immunol 10: 208, 2019. DOI: 10.3389/fimmu.2019.00208
    OpenUrlCrossRefPubMed
  2. ↵
    1. McClure R,
    2. Massari P
    : TLR-dependent human mucosal epithelial cell responses to microbial pathogens. Front Immunol 5: 386, 2014. DOI: 10.3389/fimmu.2014.00386
    OpenUrlCrossRefPubMed
  3. ↵
    1. Duan T,
    2. Du Y,
    3. Xing C,
    4. Wang HY,
    5. Wang RF
    : Toll-like receptor signaling and its role in cell-mediated immunity. Front Immunol 13: 812774, 2022. DOI: 10.3389/fimmu.2022.812774
    OpenUrlCrossRef
  4. ↵
    1. Hajishengallis G,
    2. Lambris JD
    : More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation. Immunol Rev 274(1): 233-244, 2016. DOI: 10.1111/imr.12467
    OpenUrlCrossRefPubMed
  5. ↵
    1. Deo PN,
    2. Deshmukh R
    : Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol 23(1): 122-128, 2019. DOI: 10.4103/jomfp.JOMFP_304_18
    OpenUrlCrossRefPubMed
  6. ↵
    1. Fan Y,
    2. Wu L,
    3. Zhai B
    : The mycobiome: interactions with host and implications in diseases. Curr Opin Microbiol 75: 102361, 2023. DOI: 10.1016/j.mib.2023.102361
    OpenUrlCrossRef
  7. ↵
    1. Gow NAR,
    2. Latge JP,
    3. Munro CA
    : The fungal cell wall: structure, biosynthesis, and function. Microbiol Spectr 5(3), 2017. DOI: 10.1128/microbiolspec.FUNK-0035-2016
    OpenUrlCrossRefPubMed
  8. ↵
    1. Mata-Martínez P,
    2. Bergón-Gutiérrez M,
    3. Del Fresno C
    : Dectin-1 signaling update: new perspectives for trained immunity. Front Immunol 13: 812148, 2022. DOI: 10.3389/fimmu.2022.812148
    OpenUrlCrossRef
  9. ↵
    1. Hatinguais R,
    2. Willment JA,
    3. Brown GD
    : C-type lectin receptors in antifungal immunity: Current knowledge and future developments. Parasite Immunol 45(2): e12951, 2023. DOI: 10.1111/pim.12951
    OpenUrlCrossRef
  10. ↵
    1. Kerrigan AM,
    2. Brown GD
    : Syk-coupled-type lectin receptors that mediate cellular activation via single tyrosine-based activation motifs. Immunol Rev 234(1): 335-352, 2010. DOI: 10.1111/j.0105-2896.2009.00882.x
    OpenUrlCrossRefPubMed
  11. ↵
    1. Reid DM,
    2. Gow NA,
    3. Brown GD
    : Pattern recognition: recent insights from Dectin-1. Curr Opin Immunol 21(1): 30-37, 2009. DOI: 10.1016/j.coi.2009.01.003
    OpenUrlCrossRefPubMed
    1. Chung Y,
    2. Chang SH,
    3. Martinez GJ,
    4. Yang XO,
    5. Nurieva R,
    6. Kang HS,
    7. Ma L,
    8. Watowich SS,
    9. Jetten AM,
    10. Tian Q,
    11. Dong C
    : Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30(4): 576-587, 2009. DOI: 10.1016/j.immuni.2009.02.007
    OpenUrlCrossRefPubMed
  13. ↵
    1. Vautier S,
    2. Sousa Mda G,
    3. Brown GD
    : C-type lectins, fungi and Th17 responses. Cytokine Growth Factor Rev 21(6): 405-412, 2010. DOI: 10.1016/j.cytogfr.2010.10.001
    OpenUrlCrossRefPubMed
  14. ↵
    1. Cua DJ,
    2. Tato CM
    : Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10(7): 479-489, 2010. DOI: 10.1038/nri2800
    OpenUrlCrossRefPubMed
    1. Hirota K,
    2. Duarte JH,
    3. Veldhoen M,
    4. Hornsby E,
    5. Li Y,
    6. Cua DJ,
    7. Ahlfors H,
    8. Wilhelm C,
    9. Tolaini M,
    10. Menzel U,
    11. Garefalaki A,
    12. Potocnik AJ,
    13. Stockinger B
    : Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12(3): 255-263, 2011. DOI: 10.1038/ni.1993
    OpenUrlCrossRefPubMed
    1. Gladiator A,
    2. LeibundGut-Landmann S
    : Innate lymphoid cells: new players in IL-17-mediated antifungal immunity. PLoS Pathog 9(12): e1003763, 2013. DOI: 10.1371/journal.ppat.1003763
    OpenUrlCrossRefPubMed
  17. ↵
    1. Martin B,
    2. Hirota K,
    3. Cua DJ,
    4. Stockinger B,
    5. Veldhoen M
    : Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity 31(2): 321-330, 2009. DOI: 10.1016/j.immuni.2009.06.020
    OpenUrlCrossRefPubMed
  18. ↵
    1. Plato A,
    2. Willment JA,
    3. Brown GD
    : C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways. Int Rev Immunol 32(2): 134-156, 2013. DOI: 10.3109/08830185.2013.777065
    OpenUrlCrossRefPubMed
  19. ↵
    1. Tangye SG,
    2. Puel A
    : The Th17/IL-17 axis and host defense against fungal infections. J Allergy Clin Immunol Pract 11(6): 1624-1634, 2023. DOI: 10.1016/j.jaip.2023.04.015
    OpenUrlCrossRef
  20. ↵
    1. Ferwerda B,
    2. Ferwerda G,
    3. Plantinga TS,
    4. Willment JA,
    5. van Spriel AB,
    6. Venselaar H,
    7. Elbers CC,
    8. Johnson MD,
    9. Cambi A,
    10. Huysamen C,
    11. Jacobs L,
    12. Jansen T,
    13. Verheijen K,
    14. Masthoff L,
    15. Morré SA,
    16. Vriend G,
    17. Williams DL,
    18. Perfect JR,
    19. Joosten LA,
    20. Wijmenga C,
    21. van der Meer JW,
    22. Adema GJ,
    23. Kullberg BJ,
    24. Brown GD,
    25. Netea MG
    : Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 361(18): 1760-1767, 2009. DOI: 10.1056/NEJMoa0901053
    OpenUrlCrossRefPubMed
    1. Glocker EO,
    2. Hennigs A,
    3. Nabavi M,
    4. Schäffer AA,
    5. Woellner C,
    6. Salzer U,
    7. Pfeifer D,
    8. Veelken H,
    9. Warnatz K,
    10. Tahami F,
    11. Jamal S,
    12. Manguiat A,
    13. Rezaei N,
    14. Amirzargar AA,
    15. Plebani A,
    16. Hannesschläger N,
    17. Gross O,
    18. Ruland J,
    19. Grimbacher B
    : A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 361(18): 1727-1735, 2009. DOI: 10.1056/NEJMoa0810719
    OpenUrlCrossRefPubMed
  22. ↵
    1. Iliev ID,
    2. Funari VA,
    3. Taylor KD,
    4. Nguyen Q,
    5. Reyes CN,
    6. Strom SP,
    7. Brown J,
    8. Becker CA,
    9. Fleshner PR,
    10. Dubinsky M,
    11. Rotter JI,
    12. Wang HL,
    13. McGovern DP,
    14. Brown GD,
    15. Underhill DM
    : Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336(6086): 1314-1317, 2012. DOI: 10.1126/science.1221789
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Wada T,
    2. Maruyama R,
    3. Irie Y,
    4. Hashimoto M,
    5. Wakabayashi H,
    6. Okudaira N,
    7. Uesawa Y,
    8. Kagaya H,
    9. Sakagami H
    : In vitro anti-tumor activity of azulene amide derivatives. In Vivo 32(3): 479-486, 2018. DOI: 10.21873/invivo.11264
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Inomata M,
    2. Amano S,
    3. Abe M,
    4. Hayashi T,
    5. Sakagami H
    : Innate immune response of human periodontal ligament fibroblasts via the Dectin-1/Syk pathway. J Med Microbiol 71(12), 2022. DOI: 10.1099/jmm.0.001627
    OpenUrlCrossRef
  25. ↵
    1. Inomata M,
    2. Xu S,
    3. Chandra P,
    4. Meydani SN,
    5. Takemura G,
    6. Philips JA,
    7. Leong JM
    : Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging. Proc Natl Acad Sci U S A 117(52): 33561-33569, 2020. DOI: 10.1073/pnas.2015368117
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Uehara A,
    2. Sugawara S,
    3. Takada H
    : Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans. J Med Microbiol 51(8): 626-634, 2002. DOI: 10.1099/0022-1317-51-8-626
    OpenUrlCrossRefPubMed
  27. ↵
    1. Marín-Rubio JL,
    2. Raote I,
    3. Inns J,
    4. Dobson-Stone C,
    5. Rajan N
    : CYLD in health and disease. Dis Model Mech 16(6): dmm050093, 2023. DOI: 10.1242/dmm.050093
    OpenUrlCrossRef
  28. ↵
    1. Priem D,
    2. van Loo G,
    3. Bertrand MJ
    : A20 and cell death-driven inflammation. Trends Immunol 41(5): 421-435, 2020. DOI: 10.1016/j.it.2020.03.001
    OpenUrlCrossRef
  29. ↵
    1. Tang C,
    2. Kamiya T,
    3. Liu Y,
    4. Kadoki M,
    5. Kakuta S,
    6. Oshima K,
    7. Hattori M,
    8. Takeshita K,
    9. Kanai T,
    10. Saijo S,
    11. Ohno N,
    12. Iwakura Y
    : Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine. Cell Host Microbe 18(2): 183-197, 2015. DOI: 10.1016/j.chom.2015.07.003
    OpenUrlCrossRefPubMed
  30. ↵
    1. Cohen-Kedar S,
    2. Baram L,
    3. Elad H,
    4. Brazowski E,
    5. Guzner-Gur H,
    6. Dotan I
    : Human intestinal epithelial cells respond to beta-glucans via Dectin-1 and Syk. Eur J Immunol 44(12): 3729-3740, 2014. DOI: 10.1002/eji.201444876
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Dectin-1/SYK Activation Induces Antimicrobial Peptide and Negative Regulator of NF-κB Signaling in Human Oral Epithelial Cells
MEGUMI INOMATA, MASAYO ABE, YASUKO KAWASE, TORU HAYASHI, SHIGERU AMANO, HIROSHI SAKAGAMI
In Vivo May 2024, 38 (3) 1042-1048; DOI: 10.21873/invivo.13537
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords