Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
January-2022 Volume 23 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2022 Volume 23 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in Talaromyces marneffei infection

  • Authors:
    • Yang Peng
    • Yan Chen
    • Jinhong Ma
    • Wei Zhou
    • Yangyang Wang
    • Yuyue Wang
    • Hui Zheng
    • Weifeng Shi
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215000, P.R. China
    Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 84
    |
    Published online on: November 25, 2021
       https://doi.org/10.3892/etm.2021.11007
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Dendritic cell‑associated C‑type lectin‑1 (Dectin‑1), a C‑type lectin receptor, serves a critical role in host antifungal immunity. However, the molecular mechanism and function of Dectin‑1‑mediated signaling in response to infection by the pathogenic fungus Talaromyces marneffei remains unclear. To understand the role of Dectin‑1 signaling against T. marneffei infection, the phosphorylation of spleen tyrosine kinase (Syk), nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor, α (IκBα) and NF‑κB were analyzed using western blotting, and the secretion of cytokines was detected using ELISA. Upon sporular or hyphal heat‑killed T. marneffei stimulation, Dectin‑1 in THP‑1 macrophages recognized and induced the activation of Syk, and in turn triggered phosphorylation of downstream molecules IκBα and NF‑κB, thus increasing the secretion of TNF‑α and IL‑8. Conversely, knockdown of Dectin‑1 in THP‑1 macrophages downregulated the phosphorylation of Syk, IκBα and NF‑κB molecules, and significantly decreased the production of TNF‑α and IL‑8. These results indicated that Dectin‑1 may have a crucial role in inducing the inflammatory response via increasing levels of TNF‑α and IL‑8 induced by T. marneffei, whereas NF‑κB may be the key downstream molecule involved in the response to T. marneffei infection. Subsequently, THP‑1 macrophages could orchestrate the innate immune system by releasing the cytokines TNF‑α and IL‑8. Therefore, it was hypothesized that regulation of the Dectin‑1 signaling pathway may effectively interfere with the defense ability of the host against T. marneffei infection.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Capponi M, Segretain G and Sureau P: Penicillosis from Rhizomys sinensis. Bull Soc Pathol Exot Filiales. 49:418–421. 1956.PubMed/NCBI(In French).

2 

Segretain G: Penicillium marneffei n.sp., agent of a mycosis of the reticuloendothelial system. Mycopathol Mycol Appl. 11:327–353. 1959.PubMed/NCBI View Article : Google Scholar : (In French).

3 

Boyce KJ and Andrianopoulos A: Fungal dimorphism: The switch from hyphae to yeast is a specialized morphogenetic adaptation allowing colonization of a host. FEMS Microbiol Rev. 39:797–811. 2015.PubMed/NCBI View Article : Google Scholar

4 

Cogliati M, Roverselli A, Boelaert JR, Taramelli D, Lombardi L and Viviani MA: Development of an in vitro macrophage system to assess Penicillium marneffei growth and susceptibility to nitric oxide. Infect Immun. 65:279–284. 1997.PubMed/NCBI View Article : Google Scholar

5 

Tsang CC, Lau SKP and Woo PCY: Sixty Years from Segretain's Description: What Have We Learned and Should Learn About the Basic Mycology of Talaromyces marneffei? Mycopathologia. 184:721–729. 2019.PubMed/NCBI View Article : Google Scholar

6 

Hu Y, Zhang J, Li X, Yang Y, Zhang Y, Ma J and Xi L: Penicillium marneffei infection: An emerging disease in mainland China. Mycopathologia. 175:57–67. 2013.PubMed/NCBI View Article : Google Scholar

7 

Le T, Huu Chi N, Kim Cuc NT, Manh Sieu TP, Shikuma CM, Farrar J and Day JN: AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis. 51:1458–1462. 2010.PubMed/NCBI View Article : Google Scholar

8 

Sellge G and Kufer TA: PRR-signaling pathways: Learning from microbial tactics. Semin Immunol. 27:75–84. 2015.PubMed/NCBI View Article : Google Scholar

9 

Akira S, Uematsu S and Takeuchi O: Pathogen recognition and innate immunity. Cell. 124:783–801. 2006.PubMed/NCBI View Article : Google Scholar

10 

Salazar F and Brown GD: Antifungal Innate Immunity: A Perspective from the Last 10 Years. J Innate Immun. 10:373–397. 2018.PubMed/NCBI View Article : Google Scholar

11 

Goyal S, Castrillón-Betancur JC, Klaile E and Slevogt H: The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors. Front Immunol. 9(1261)2018.PubMed/NCBI View Article : Google Scholar

12 

Sancho D and Reis e Sousa C: Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol. 30:491–529. 2012.PubMed/NCBI View Article : Google Scholar

13 

Saijo S and Iwakura Y: Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol. 23:467–472. 2011.PubMed/NCBI View Article : Google Scholar

14 

Wevers BA, Kaptein TM, Zijlstra-Willems EM, Theelen B, Boekhout T, Geijtenbeek TB and Gringhuis SI: Fungal engagement of the C-type lectin mincle suppresses dectin-1-induced antifungal immunity. Cell Host Microbe. 15:494–505. 2014.PubMed/NCBI View Article : Google Scholar

15 

Brown GD: Dectin-1: A signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 6:33–43. 2006.PubMed/NCBI View Article : Google Scholar

16 

Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, et al: Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity. 32:681–691. 2010.PubMed/NCBI View Article : Google Scholar

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

18 

Limper AH, Adenis A, Le T and Harrison TS: Fungal infections in HIV/AIDS. Lancet Infect Dis. 17:e334–e343. 2017.PubMed/NCBI View Article : Google Scholar

19 

Nakamura K, Miyazato A, Koguchi Y, Adachi Y, Ohno N, Saijo S, Iwakura Y, Takeda K, Akira S and Fujita J: Toll-like receptor 2 (TLR2) and dectin-1 contribute to the production of IL-12p40 by bone marrow-derived dendritic cells infected with Penicillium marneffei. Microbes Infect. 10:1223–1227. 2008.PubMed/NCBI View Article : Google Scholar

20 

Gantner BN, Simmons RM, Canavera SJ, Akira S and Underhill DM: Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 197:1107–1117. 2003.PubMed/NCBI View Article : Google Scholar

21 

Sun WK, Lu X, Li X, Sun QY, Su X, Song Y, Sun HM and Shi Y: Dectin-1 is inducible and plays a crucial role in Aspergillus-induced innate immune responses in human bronchial epithelial cells. Eur J Clin Microbiol Infect Dis. 31:2755–2764. 2012.PubMed/NCBI View Article : Google Scholar

22 

Cohen-Kedar S, Baram L, Elad H, Brazowski E, Guzner-Gur H and Dotan I: Human intestinal epithelial cells respond to β-glucans via Dectin-1 and Syk. Eur J Immunol. 44:3729–3740. 2014.PubMed/NCBI View Article : Google Scholar

23 

Hayden MS and Ghosh S: Shared principles in NF-kappaB signaling. Cell. 132:344–362. 2008.PubMed/NCBI View Article : Google Scholar

24 

Hinz M and Scheidereit C: The IκB kinase complex in NF-κB regulation and beyond. EMBO Rep. 15:46–61. 2014.PubMed/NCBI View Article : Google Scholar

25 

Zhu LL, Zhao XQ, Jiang C, You Y, Chen XP, Jiang YY, Jia XM and Lin X: C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity. 39:324–334. 2013.PubMed/NCBI View Article : Google Scholar

26 

Sun H, Xu XY, Tian XL, Shao HT, Wu XD, Wang Q, Su X and Shi Y: Activation of NF-κB and respiratory burst following Aspergillus fumigatus stimulation of macrophages. Immunobiology. 219:25–36. 2014.PubMed/NCBI View Article : Google Scholar

27 

Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, et al: Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 22:507–517. 2005.PubMed/NCBI View Article : Google Scholar

28 

Duan Z, Chen X, Du L, Liu C, Zeng R, Chen Q and Li M: Inflammation Induced by Candida parapsilosis in THP-1 Cells and Human Peripheral Blood Mononuclear Cells (PBMCs). Mycopathologia. 182:1015–1023. 2017.PubMed/NCBI View Article : Google Scholar

29 

Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC and Geijtenbeek TB: Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat Immunol. 10:203–213. 2009.PubMed/NCBI View Article : Google Scholar

30 

Koh TJ and DiPietro LA: Inflammation and wound healing: The role of the macrophage. Expert Rev Mol Med. 13(e23)2011.PubMed/NCBI View Article : Google Scholar

31 

Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT and Sahebkar A: Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 233:6425–6440. 2018.PubMed/NCBI View Article : Google Scholar

32 

Idriss HT and Naismith JH: TNF alpha and the TNF receptor superfamily: Structure-function relationship(s). Microsc Res Tech. 50:184–195. 2000.PubMed/NCBI View Article : Google Scholar

33 

Aggarwal BB, Gupta SC and Kim JH: Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 119:651–665. 2012.PubMed/NCBI View Article : Google Scholar

34 

Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, Duan S, Eiwegger T, Eljaszewicz A, Ferstl R, et al: Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 138:984–1010. 2016.PubMed/NCBI View Article : Google Scholar

35 

Zhang W and Chen H: The study on the interleukin-8 (IL-8)]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 19:697–702. 2002.PubMed/NCBI(In Chinese).

36 

Li M, Liu ZH, Chen Q, Zhou WQ, Yu MW, Lü GX, Lü XL, Shen YN, Liu WD and Wu SX: Insoluble beta-glucan from the cell wall of Candida albicans induces immune responses of human THP-1 monocytes through Dectin-1. Chin Med J (Engl). 122:496–501. 2009.PubMed/NCBI

37 

Hohl TM, Van Epps HL, Rivera A, Morgan LA, Chen PL, Feldmesser M and Pamer EG: Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display. PLoS Pathog. 1(e30)2005.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Peng Y, Chen Y, Ma J, Zhou W, Wang Y, Wang Y, Zheng H and Shi W: Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection. Exp Ther Med 23: 84, 2022.
APA
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y. ... Shi, W. (2022). Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection. Experimental and Therapeutic Medicine, 23, 84. https://doi.org/10.3892/etm.2021.11007
MLA
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y., Zheng, H., Shi, W."Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection". Experimental and Therapeutic Medicine 23.1 (2022): 84.
Chicago
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y., Zheng, H., Shi, W."Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection". Experimental and Therapeutic Medicine 23, no. 1 (2022): 84. https://doi.org/10.3892/etm.2021.11007
Copy and paste a formatted citation
x
Spandidos Publications style
Peng Y, Chen Y, Ma J, Zhou W, Wang Y, Wang Y, Zheng H and Shi W: Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection. Exp Ther Med 23: 84, 2022.
APA
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y. ... Shi, W. (2022). Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection. Experimental and Therapeutic Medicine, 23, 84. https://doi.org/10.3892/etm.2021.11007
MLA
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y., Zheng, H., Shi, W."Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection". Experimental and Therapeutic Medicine 23.1 (2022): 84.
Chicago
Peng, Y., Chen, Y., Ma, J., Zhou, W., Wang, Y., Wang, Y., Zheng, H., Shi, W."Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection". Experimental and Therapeutic Medicine 23, no. 1 (2022): 84. https://doi.org/10.3892/etm.2021.11007
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team