Razieh Tavakoli Oliaee1, Iraj Sharifi2, Ali Afgar3, Abdollah Jafarzadeh4, Amir Tavakoli Kareshk5, Mehdi Bamorovat6, Hamid Sharifi7, Zahra Babaei8, Amir Keyhani1, Alireza Keyhani6, Leili Abedi9, Fatemeh Sharifi10. 1. Department of Medical Parasitology and Mycology, Kerman University of Medical Sciences, Kerman, Iran. 2. Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: iraj.sharifi@yahoo.com. 3. Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran. 4. Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran. 5. Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran. 6. Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. 7. HIV/STI Surveillance Research Center, WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran. 8. Department of Medical Parasitology and Mycology, Kerman University of Medical Sciences, Kerman, Iran; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran. 9. Department of Statistics and Epidemiology, Faculty of Health, Kerman University of Medical Sciences, Kerman, Iran. 10. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Abstract
BACKGROUND: Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated. METHODS: In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined. RESULTS: L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones. CONCLUSIONS: The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.
BACKGROUND: Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated. METHODS: In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined. RESULTS:L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones. CONCLUSIONS: The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.