Document Type: Original Article

Authors

1 Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences,

2 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

6 Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Toll like receptors play a major role in immune responses against Leishmania parasites. Objective: To evaluate the efficacy of vaccination with live attenuated L. major and TLR4 agonist in protection against L. major infection. Methods: Attenuated L. major was prepared by continuous sub-culturing of the parasite. A total of 90 mice were assigned to 9 groups including 6 groups of BALB/c (G1-6) and 3 groups (G7-9) of C57BL/6 mice. Group 1 was the control groups, group 2 received the wild-type L. major promastigotes, group 3 the attenuated line, group 4 the TLR4 agonist, group 5 the wild-type L. major and TLR4 agonist, and group 6 the attenuated line along with TLR4 agonist. Group 7 was control, group 8 received wild-type L. major and group 9 the wild-type along with TLR4 agonist. Vaccinated mice were then challenged with wild-type of L. major. Lesion size, parasite burden, and the expression levels of IL-4, IFN-γ, IL-2, 1L-17A, IL-10, TGF-β and TLR4 were evaluated before the challenge while parasite burden and lesion size were evaluated. Results: Vaccinated mice with a TLR4 agonist or attenuated L. major plus TLR4 agonist produced the highest levels of IFN-γ, IL-2, and IL-17A. Post-challenge analysis revealed that mice vaccinated with the attenuated line along with TLR4 agonist displayed the lowest lesion size and parasite load. These mice developed a predominant Th1 immune response. Conclusion: Vaccination with the attenuated L. major along with TLR4 agonist promotes a Th1-mediated immune response which leads to the protection of BALB/c mice against L. major infection.

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