N Ahmadi1, A Ahmadi2, E Kheirali3, M Hossein Yadegari4, M Bayat5, A Shajiei6, A Ali Amini7, S Ashrafi8, M Abolhassani3, S Faezi9, S Amir Yazdanparast10, M Mahdavi11. 1. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran; Department of Microbiology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran. 2. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran; Department of Veterinary Medicine, Islamic Azad University, Karaj, Iran. 3. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran. 4. Department of Mycology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran. 5. Department of Microbiology, Faculty of Veterinary Specialized Sciences, Islamic Azad University Science and Research Branch, Tehran, Iran. 6. Immunology Lab, Bu Ali Research Institute, Mashhad University of Medical sciences, Mashhad, Iran. 7. Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. 8. Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran. 9. Medical Biotechnology Research Center, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran. 10. Department of Medical Parasitology and Mycology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Sayazdan@yahoo.com. 11. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran; Recombinant Vaccine Research Center, Tehran university of Medical Sciences, Tehran, Iran. Electronic address: M_Mahdavi@pasteur.ac.ir.
Abstract
OBJECTIVE: The effect of candidemia on immunologic parameters in breast tumor bearing patients is not well studied. Here, we hypothesised that candidemia in the tumor background may change the outcome of immunologic parameters and tumor condition. METHOD: Mice were divided into four groups, including normal, tumor, Candida infected (only Candidiasis) and tumor/Candidiasis groups. Tumor changes were recorded daily after tumor transplantation and induction of candidemia. Splenocytes of mice were harvested, cultured, and stimulated with PHA; afterwards, IL-4, IL-10, IFN-γ, TNF-α and TGF-β cytokines were assessed using ELISA kits. We also evaluated the population of CD4+CD25+Foxp3+ regulatory T cells in the tumor infiltrated and splenocytes. RESULTS: The results showed that infection with C. albicans decreased the IFN-γ/IL-4 ratio in tumor/candidiasis and candidiasis groups versus their non-infected controls. IL-10, TGF-β and TNF-α levels increased in the candidiasis group. In addition, Candidemia led to an increase in the Treg population in tumor microenvironment and splenocytes of experimental groups compared with non-infected controls. Finally, candidemia increased tumor growth of tumor/Candidiasis group compared with the tumor group. CONCLUSION: It seems that systemic infection with C. albicans could not only induce regulatory T cells but also result in dysregulation of cytokine network and thereby facilitate tumor growth.
OBJECTIVE: The effect of candidemia on immunologic parameters in breast tumor bearing patients is not well studied. Here, we hypothesised that candidemia in the tumor background may change the outcome of immunologic parameters and tumor condition. METHOD:Mice were divided into four groups, including normal, tumor, Candida infected (only Candidiasis) and tumor/Candidiasis groups. Tumor changes were recorded daily after tumor transplantation and induction of candidemia. Splenocytes of mice were harvested, cultured, and stimulated with PHA; afterwards, IL-4, IL-10, IFN-γ, TNF-α and TGF-β cytokines were assessed using ELISA kits. We also evaluated the population of CD4+CD25+Foxp3+ regulatory T cells in the tumor infiltrated and splenocytes. RESULTS: The results showed that infection with C. albicans decreased the IFN-γ/IL-4 ratio in tumor/candidiasis and candidiasis groups versus their non-infected controls. IL-10, TGF-β and TNF-α levels increased in the candidiasis group. In addition, Candidemia led to an increase in the Treg population in tumor microenvironment and splenocytes of experimental groups compared with non-infected controls. Finally, candidemia increased tumor growth of tumor/Candidiasis group compared with the tumor group. CONCLUSION: It seems that systemic infection with C. albicans could not only induce regulatory T cells but also result in dysregulation of cytokine network and thereby facilitate tumor growth.
Authors: Christian Ortega-Loubon; Beatriz Cano-Hernández; Rodrigo Poves-Alvarez; María Fe Muñoz-Moreno; Patricia Román-García; Sara Balbás-Alvarez; Olga de la Varga-Martínez; Esther Gómez-Sánchez; Estefanía Gómez-Pesquera; Mario Lorenzo-López; Eduardo Tamayo; María Heredia-Rodríguez Journal: J Clin Med Date: 2019-09-20 Impact factor: 4.241