The Effect of Cyclophosphamide on TLR2 Gene Expression in Balb/c Mice with Systemic Candidiasis

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Medical Mycology and Parasitology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Medical Mycology and Parasitology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Assistant Professor, Department of Medical Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran

5 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Toll like receptor-2 (TLR2) plays an important role in the process of detection and launching the immune response against Candida albicans. Cyclophosphamide is one of the most widely used chemotherapy drugs, which causes severe neutropenia and suppression of the immune system. In this study Balb/c mice were infected to disseminated candidiasis and neutropenia and expression of TLR2 gene was measured in whole blood samples of each mice.Methods: Twenty-eight mice were divided into 4 groups and injected with Cyclophosphamide and C. albicans. Blood samples were used for RNA extraction and cDNA synthesis, and expression of TLR2 gene was measured by real-time polymerase chain reaction (Real-time PCR). Statistical analysis was performed using Kruskal-Wallis and 2-∆∆CT method.Findings: Gene expression was increased in the group receiving Candida albicans and also in group receiving both Cyclophosphamide and Candida albicans but decreased in the group just receiving Cyclophosphamide.Conclusion: There was no significant difference between the control group and experimental groups for TLR2 gene expression (P = 0.478). However, the results of this study can be regarding in selecting TLR2 or its receptor as a therapeutic target with monoclonal antibodies or gene therapy techniques.

Keywords

References

  1. Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche HU, Quan SP, et al. Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance(R)) registry, 2004-2008. Diagn Microbiol Infect Dis 2012; 74(4): 323-31.
  2. Quindos G. Epidemiology of candidaemia and invasive candidiasis. A changing face. Rev Iberoam Micol 2014; 31(1): 42-8.
  3. Diekema D, Arbefeville S, Boyken L, Kroeger J, Pfaller M. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis 2012; 73(1): 45-8.
  4. Wisplinghoff H, Ebbers J, Geurtz L, Stefanik D, Major Y, Edmond MB, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents 2014; 43(1): 78-81.
  5. Louie A, Deziel M, Liu W, Drusano MF, Gumbo T, Drusano GL. Pharmacodynamics of caspofungin in a murine model of systemic candidiasis: importance of persistence of caspofungin in tissues to understanding drug activity. Antimicrob Agents Chemother 2005; 49(12): 5058-68.
  6. Moser SA, Domer JE. Effects of cyclophosphamide on murine candidiasis. Infect Immun 1980; 27(2): 376-86.
  7. Deshpande A, Gaur S, Bal AM. Candidaemia in the non-neutropenic patient: a critique of the guidelines. Int J Antimicrob Agents 2013; 42(4): 294-300.
  8. Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag 2014; 10: 95-105.
  9. Colvin M, Hilton J. Pharmacology of cyclophosphamide and metabolites. Cancer Treat Rep 1981; 65 Suppl 3: 89-95.
  10. Zhang J, Tian Q, Zhou SF. Clinical Pharmacology of Cyclophosphamide and Ifosfamide. Curr Drug ther 2006; 1(1): 55-84.
  11. Abbas AK, Lichtman AHH, Pillai S. Cellular and Molecular immunology. 7th ed. Philadelphia, PA: Saunders; 2011.
  12. Reales-Calderon JA, Sylvester M, Strijbis K, Jensen ON, Nombela C, Molero G, et al. Candida albicans induces pro-inflammatory and anti-apoptotic signals in macrophages as revealed by quantitative proteomics and phosphoproteomics. J Proteomics 2013; 91: 106-35.
  13. Quintin J, Saeed S, Martens JH, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 2012; 12(2): 223-32.
  14. Romani L. Immunity to fungal infections. Nat Rev Immunol 2011; 11(4): 275-88.
  15. Moresco EM, LaVine D, Beutler B. Toll-like receptors. Curr Biol 2011; 21(13): R488-R493.
  16. Bellocchio S, Montagnoli C, Bozza S, Gaziano R, Rossi G, Mambula SS, et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol 2004; 172(5): 3059-69.
  17. Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun 2009; 388(4): 621625.
  18. Netea MG, Sutmuller R, Hermann C, Van der Graaf CA, van der Meer JW, van Krieken JH, et al. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol 2004; 172(6): 3712-8.
  19. Steinhagen F, Kinjo T, Bode C, Klinman DM. TLR-based immune adjuvants. Vaccine 2011; 29(17): 3341-55.
  20. Ferwerda G, Netea MG, Joosten LA, van der Meer JW, Romani L, Kullberg BJ. The role of Toll-like receptors and C-type lectins for vaccination against Candida albicans. Vaccine 2010; 28(3): 614-22.
  21. Lawlor H, Meunier A, McDermott N, Lynch TH, Marignol L. Identification of suitable endogenous controls for gene and miRNA expression studies in irradiated prostate cancer cells. Tumour Biol 2015; 36(8): 6019-28.
  22. Katzung B, Trevor A. Basic and Clinical Pharmacology. 13th ed. New York, NY: McGraw-Hill; 2014.
  23. Blasi E, Mucci A, Neglia R, Pezzini F, Colombari B, Radzioch D, et al. Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans. FEMS Immunol Med Microbiol 2005; 44(1): 69-79.
  24. Villamon E, Gozalbo D, Roig P, O'Connor JE, Fradelizi D, Gil ML. Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes Infect 2004; 6(1): 1-7.
Journal of Isfahan Medical School
Volume 34, Issue 389 - Serial Number 389
May and June 2016
Pages 769-774

Files

History

  • Receive Date: 02 February 2016
  • Revise Date: 03 May 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics