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Abstract

This study aimed to investigate the effect of immune stimulation by sonicated fungal antigens of Cryptococcus adeliensis using chitosan nanoparticles in rats treated with high doses of antibiotics. For this purpose, sixty rats of both sexes were divided randomly into six groups (10 animals, both males and females, in each group), as following: (G1) immunized with 0.5ml whole sonicated fungal Ag (0.83mg/ml protein concentration) /SC, 2 dose / 2 weeks interval. 2nd group (G2) immunized with 0.5ml whole fungal Ag as G1 and treated daily with high doses of antibiotic for six weeks (gentamicin 0.5mg/mL). 3rd group (G3) immunized I\P, with whole fungal Ag mixed with chitosan nanoparticles (1:1) 0.5 ml, 2 dose / 2 weeks intervals and treated with antibiotic as 2nd group, and (G4) was served as control positive group and (G5) was treated with antibiotic as 2nd group, and sixth group (G6) was served as negative control inoculated with normal saline 0.3ml.  At 27 and 30 days post-immunization, skin test was done in 1st, 2nd, 3rd, and 5th groups and blood samples were collected to measure the serum level of antibody titers, after those animals of G1, G2, G3, G4, and G5 were inoculated SC, with 0.3ml, containing 1x108 of the fungal cell, and the sixth group was injected with 0.3ml normal saline I/P. At 4 weeks post-infection. All animals were sacrificed and pieces of tissues were removed from the liver, lung, kidney, and brain for histopathological examination. The result revealed a high mean of skin thickness and high serum antibody titers in immunized animals but in 2nd group, the antibiotic treatment led to depressing values of skin test (ns) and serum of antibody titers (ns). Chitosan nanoparticles can improve values of skin test (***) and serum of antibody titers (***) in the 3rd group. The histopathological result showed severe pathological lesions in examined organs of the positive control group and severe lesions in these organs in animals treated with antibiotics post-infection. In addition, the current result showed mild to moderate lesions in examined organs of immunized animals with moderate lesions in immunized animal’s treatment with antibiotics post-infection. The immunized animals with mixed fungal antigens and chitosan nanoparticles and treatment with antibiotics express mild to no clear lesions in examined organs post-infection. As a conclusion, the prolonged high doses of antibiotics lead to depressing immune response in immunized animal,s while immunized animals with fungal antigens mixed with chitosan nanoparticles can improve the immune response.

Keywords

Rat Immune system Chitosan nanoparticle Serum antibody

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The authors transfer the copyrights of their papers to the Iranian Society of Ichthyology. However, the information could be used in accordance with the Creative Commons licence (Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

How to Cite
Hamza, B. S. ., & ALWAN, M. J. (2022). Immunopathological effect of Cryptococcus adeliensis in treated rats with chitosan nanoparticles and antibiotics. Iranian Journal of Ichthyology, 9, 424–438. Retrieved from https://ijichthyol.org/index.php/iji/article/view/841
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References

  1. Abd Elgadir, M.; Uddin, M.S.; Ferdosh, S.; Adam, A.; Chowdhury, A.J.K. & Sarker, M.Z.I. 2015. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review. Journal of Food and Drug Analysis 23(4): 619-629.
  2. Baker, R.D. & Haugen, R.K. 1955. Tissue changes and tissue diagnosis in cryptococcosis. A study of 26 cases. American Journal of Clinical Pathology 25(1): 1243.
  3. Brown, G.D. 2012. Innate antifungal immunity. 3: 1–21.
  4. Brown, G.D.; Denning, D.W.; Gow, N.A.; Levitz, S. M.; Netea, M.G. & White, T.C. 2012. Hidden killers: human fungal infections. Science Translational Medicine 4(165): 165rv13-165rv13.
  5. Bueter, C.L.; Lee, C.K.; Wang, J.P.; Ostroff, G.R.; Specht, C.A. & Levitz, S.M. 2014. Spectrum and mechanisms of inflammasome activation by chitosan. The Journal of Immunology 192(12): 5943-5951.
  6. Cassone, A. & Casadevall, A. 2012. Recent progress in vaccines against fungal diseases. Current Opinion in Microbiology 15(4): 427-433.
  7. Castro-Lainez, M.T.; Deliz-Aguirre, R.; Antunez, D.; Cruz-Codina, M.; Cahuayme-Zuniga, L.; Vitale, K. & Midturi, J.K. 2019. Cryptococcus laurentii meningitis in a non-HIV patient. IDCases 18: e00612.
  8. Choe, Y.J.; Blatt, D.B.; Yalcindag, A.; Geffert, S.F.; Bobenchik, A.M. & Michelow, I.C. 2020. Cryptococcus albidus fungemia in an immune-suppressed child: case report and systematic literature review. Journal of the Pediatric Infectious Diseases Society 9(1): 100-105.
  9. Chowdhary, A.; Sharma, C. & Meis, J.F. 2017. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLOS Pathogens 13(5): e1006290.
  10. Coelho, C.; Bocca, A.L. & Casadevall, A. 2014. The intracellular life of Cryptococcus neoformans. Annual Review of Pathology 9: 219.
  11. De Vadder, F.; Kovatcheva-Datchary, P.; Goncalves, D.; Vinera, J.; Zitoun, C.; Duchampt, A. & Mithieux, G. 2014. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156(1-2): 84-96.
  12. Dromer, F.; Casadevall, A.; Perfect, J. & Sorrell, T. 2010. Cryptococcus neoformans: latency and disease. Cryptococcus: from human pathogen to model. Yeast 429-439.
  13. Ekmekciu, I.; Von Klitzing, E.; Fiebiger, U.; Escher, U.; Neumann, C.; Bacher, P. & Heimesaat, M.M. 2017. Immune responses to broad-spectrum antibiotic treatment and fecal microbiota transplantation in mice. Frontiers in Immunology 8: 397.
  14. Garcia-Hermoso, D.; Janbon, G. & Dromer, F. 1999. Epidemiological evidence for dormant Cryptococcus neoformans infection. Journal of Clinical Microbiology 37(10): 3204-3209.
  15. Goldman, D.; Song, X.; Kitai, R.; Casadevall, A.; Zhao, M.L. & Lee, S.C. 2001. Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia: role of specific antibody and soluble capsular polysaccharide. Infection and Immunity 69(3): 1808-1815.
  16. Gozalbo, D.; Maneu, V. & Gil, M.L. 2014. Role of IFN-gamma in immune responses to Candida albicans infections. Frontiers in Bioscience-Landmark 19(8): 1279-1290.
  17. Hassan, A.A.; Abo-Zaid, K.F. & Oraby, N.H. 2020. Molecular and conventional detection of antimicrobial activity of zinc oxide nanoparticles and cinnamon oil against Escherichia coli and Aspergillus flavus. Advances in Animal and Veterinary Sciences 8(8): 839-847.‏
  18. Ikeda-Dantsuji, Y.; Ohno, H., Tanabe, K., Umeyama, T.; Ueno, K.; Nagi, M. & Miyazaki, Y. 2015. Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages. Journal of Infection and Chemotherapy 21(12): 831-836.
  19. Ivanov, I.I. & Honda, K. 2012. Intestinal commensal microbes as immune modulators. Cell Host and Microbe 12(4): 496-508.
  20. Kabat, A.M.; Srinivasan, N. & Maloy, K.J. 2014. Modulation of immune development and function by intestinal microbiota. Trends in Immunology 35(11): 507-517.
  21. Kronstad, J.W.; Attarian, R.; Cadieux, B.; Choi, J.; D'souza, C.A.; Griffiths, E.J. & Wang, J. 2011. Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box. Nature reviews Microbiology 9(3): 193-203.
  22. Kwon-Chung, K.J.; Fraser, J.A.; Doering, T.L.; Wang, Z.A.; Janbon, G.; Idnurm, A. & Bahn, Y.S. 2014. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harbor Perspectives in Medicine 4(7): a019760.
  23. Lockhart, S.R.; Etienne, K.A.; Vallabhaneni, S.; Farooqi, J.; Chowdhary, A.; Govender, N.P. & Litvintseva, A.P. 2017. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clinical Infectious Diseases 64(2): 134-140.
  24. Maeda, Y. & Kimura, Y. 2004. Antitumor effects of various low-molecular-weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180–bearing mice. The Journal of Nutrition 134(4): 945-950.
  25. Mahmood, F.A. 2014. Study the immunomodulatory effect of chitosan on mice experimentally infected with Cryptococcus neoformans isolated from human skin lesions,” Msc. Thesis. College of Veterinary Medicine, University of Baghdad pp. 100-102.
  26. May, R.C.; Stone, N. R.; Wiesner, D.L.; Bicanic, T. & Nielsen, K. 2016. Cryptococcus: from environmental saprophyte to global pathogen. Nature Reviews Microbiology 14(2): 106-117.
  27. Medici, N.P. & Del Poeta, M. 2015. New insights on the development of fungal vaccines: from immunity to recent challenges. Memórias do Instituto Oswaldo Cruz 110: 966-973.
  28. Navalkele, B.D.; Revankar, S. & Chandrasekar, P. 2017. Candida auris: a worrisome, globally emerging pathogen. Expert Review of Anti-infective Therapy 15(9): 819-827.
  29. O'Hara, A.M. & Shanahan, F. 2006. The gut flora as a forgotten organ. EMBO Reports 7(7): 688-693.
  30. Olszewski, M.A.; Zhang, Y. & Huffnagle, G.B. 2010. Mechanisms of cryptococcal virulence and persistence. Future Microbiology 5(8): 1269-1288.
  31. Osterholzer, J.J.; Surana, R.; Milam, J.E.; Montano, G.T.; Chen, G.H.; Sonstein, J. & Olszewski, M.A. 2009. Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung. The American Journal of Pathology 174(3): 932-943.
  32. Pagán, A.J. & Ramakrishnan, L. 2018. The formation and function of granulomas. Annual Review of Immunology 36: 639-665.
  33. Park, B.J.; Wannemuehler, K.A.; Marston, B.J.; Govender, N.; Pappas, P.G. & Chiller, T.M. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. Aids 23(4): 525-530.
  34. Rosen, G.M.; Pou, S.; Ramos, C.L.; Cohen, M.S. & Britigan, B.E. 1995. Free radicals and phagocytic cells. The FASEB Journal 9(2): 200-209.
  35. Sabiiti, W.; Robertson, E.; Beale, M.A.; Johnston, S.A.; Brouwer, A.E.; Loyse, A. & Bicanic, T. 2014. Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis. The Journal of Clinical Investigation 124(5): 2000-2008.
  36. Saha, D.C.; Goldman, D.L.; Shao, X.; Casadevall, A.; Husain, S.; Limaye, A.P. & Singh, N. 2007. Serologic evidence for reactivation of cryptococcosis in solid-organ transplant recipients. Clinical and Vaccine Immunology 14(12): 1550-1554.
  37. Saijo, T.; Chen, J.; Chen, S.C.A.; Rosen, L.B.; Yi, J.; Sorrell, T.C. & Kwon-Chung, K.J. 2014. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. MBio 5(2): e00912-14.
  38. Sandini, S.; La Valle, R.; Deaglio, S.; Malavasi, F.; Cassone, A. & De Bernardis, F. 2011. A highly immunogenic recombinant and truncated protein of the secreted aspartic proteases family (rSap2t) of Candida albicans as a mucosal anticandidal vaccine. FEMS Immunology & Medical Microbiology 62(2): 215-224.
  39. Silva, L.B.; Dias, L.S.; Rittner, G.M.; Muñoz, J.E.; Souza, A.C.; Nosanchuk, J.D. & Taborda, C.P. 2017. Dendritic cells primed with Paracoccidioides brasiliensis Peptide P10 are therapeutic in immunosuppressed mice with Paracoccidioido-mycosis. Frontiers in Microbiology 8: 1057.
  40. Skene, C.D. & Sutton, P. 2006. Saponin-adjuvanted particulate vaccines for clinical use. Methods 40(1): 53-59.
  41. Tiew, P.Y.; Mac Aogain, M.; Ali, N.; Thng, K.X.; Goh, K.; Lau, K.J. & Chotirmall, S.H. 2020. The mycobiome in health and disease: emerging concepts, methodologies and challenges. Mycopathologia 185(2): 207-231.
  42. Tilg, H.; Zmora, N.; Adolph, T.E. & Elinav, E. 2020. The intestinal microbiota fuelling metabolic inflammation. Nature Reviews Immunology 20(1): 40-54.
  43. Travassos, L.R. & Taborda, C.P. 2017. Linear epitopes of Paracoccidioides brasiliensis and other fungal agents of human systemic mycoses as vaccine candidates. Frontiers in Immunology 8: 224.
  44. Van der Lubben, I.M.; Verhoef, J.C.; Borchard, G. & Junginger, H.E. 2001.Chitosan and its derivatives in mucosal drug and vaccine delivery. European Journal of Pharmaceutical Sciences 14(3): 201-207.
  45. Waldorf, A.R.; Levitz, S.M. & Diamond, R.D. 1984. In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. Journal of Infectious Diseases 150(5): 752-760.
  46. Wormley Jr, F.L.; Perfect, J.R.; Steele, C. & Cox, G.M. 2007. Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infection and Immunity 75(3): 1453-1462.
  47. Wozniak, K.L.; Young, M.L. & Wormley Jr, F.L. 2011. Protective immunity against experimental pulmonary cryptococcosis in T cell-depleted mice. Clinical and Vaccine Immunology 18(5): 717-723.
  48. Zonios, D.I.; Falloon, J.; Huang, C.Y.; Chaitt, D. & Bennett, J.E. 2007. Cryptococcosis and idiopathic CD4 lymphocytopenia. Medicine 86(2): 78-92