Original Article

Immune response in cutaneous leishmaniasis patients with healing vs. non-healing lesions

Abstract

Background and Objectives: The outcome of Leishmania infection mainly depends upon the Leishmania species which causes the disease and the generation of the type of host immune response, the healing process and protection in leishmaniasis depends upon induction of Th1 response. In this study, the Th1/Th2 cytokine profile in cutaneous leishmaniasis (CL) is evaluated.
Materials and Methods: This study was carried out in leishmaniasis clinic of CRTSDL, TUMS, during March 2018 to March 2019. Peripheral blood mononuclear cells (PBMC) of volunteers with active healing and non-healing lesion (s) of cutaneous leishmaniasis (CL), volunteers with and without history of CL were cultured and stimulated with Soluble Leishmania antigen (SLA). The supernatants were collected and the levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method.
Results: The results showed a significantly higher levels of IFN-γ in volunteers with active CL healing form (p<0.005), history of CL (p<0.005) than healthy volunteers. A significantly (p<0.005) higher level of IFN-γ was seen in volunteers with active healing form of lesion than non-healing form. There was a significantly (p<0.005) higher level of IL-10 in volunteers with a history of non-healing form and active non-healing form of CL. There was no significant difference in IL-5 production in PBMC of different groups.
Conclusion: IFN-γ production starts at early stage of cutaneous leishmaniasis and enhance during course of lesion healing, IFN-γ level is significantly higher in all patients compared to healthy volunteers, IFN-γ is significantly higher in patients with healing form than non-healing form of lesion.

1. Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012; 7(5): e35671.
2. World Health Organization (2018). Leishmaniasis. https://www.who.int/leishmaniasis/en/
3. Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386:743-800.
4. Dowlati Y. Cutaneous leishmaniasis: clinical aspect. Clin Dermatol 1996; 14:425-431.
5. Scott P, Novais FO. Cutaneous leishmaniasis: immune responses in protection and pathogenesis. Nat Rev Immunol 2016; 16:581-592.
6. Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2002; 2:845-858.
7. Choi BS, Kropf P. Evaluation of T cell responses in healing and non-healing leishmaniasis reveals differences in T helper cell polarization ex vivo and in vitro. Parasite Immunol 2009; 31:199-209.
8. Kemp K. Cytokine-producing T cell subsets in human leishmaniasis. Arch Immunol Ther Exp (Warsz) 2000; 48:173-176.
9. Castellano LR, Correia Filho D, Argiro L, Dessein H, Prata A, Dessein A, et al. Th1/Th2 immune responses are associated with active cutaneous leishmaniasis and clinical cure is associated with strong interferon-γ production. Hum Immunol 2009; 70:383-390.
10. Mahmoodi M, Khamesipour A, Dowlati Y, Rafati S, Momeni AZ, Emamjomeh M. Immune response measured in human volunteers vaccinated with autoclaved Leishmania major vaccine mixed with low dose of BCG. Clin Exp Immunol 2003; 134:303-308.
11. Ajdary S, Alimohammadian MH, Eslami MB, Kemp K, Kharazmi A. Comparison of the immune profile of nonhealing cutaneous leishmaniasis patients with those with active lesions and those who have recovered from infection. Infect Immun 2000; 68:1760-1764.
12. Habibi GR, Khamesipour A, McMaster W, Mahboudi F. Cytokine gene expression in healing and non-healing cases of cutaneous leishmaniasis in response to in vitro stimulation with recombinant gp63 using semi-quantitative RT–PCR. Scand J Immunol 2001; 54:414-420.
13. Sharifi I, Poursmaelian S, Aflatoonian MR, Ardakani RF, Mirzaei M, Fekri AR, et al. Emergence of a new focus of anthroponotic cutaneous leishmaniasis due to Leishmania tropica in rural communities of Bam district after the earthquake, Iran. Trop Med Int Health 2011; 16:510-513.
14. Bogdan C. Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats. Ann Rheum Dis 2012;71(Supp II):i60-i66.
15. Khamesipour A. Therapeutic vaccines for leishmaniasis. Expert Opin Biol Ther 2014;14:1641-1649.
16. Goto H, Lindoso JAL. Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Rev Anti Infect Ther 2010; 8: 419-433.
17. Mohammadi AMA, Khamesipour A, Khatami A, Behnia M, Eskandari SE. Cutaneous leishmaniasis in suspected patients referred to the center for research and training in skin diseases and leprosy, Tehran, Iran from 2008 to 2011. Iran J Parasitol 2013;8: 430-436.
18. Scott P, Pearce E, Natovitz P, Sher A. Vaccination against cutaneous leishmaniasis in a murine model. II. Induction of protective immunity with a soluble extract of promastigotes. J Immunol 1987; 139:221-227.
19. Salgame P. Host innate and Th1 responses and the bacterial factors that control Mycobacterium tuberculosis infection. Curr Opin Immunol 2005; 17:374-380.
20. Jafari-Shakib R, Shokrgozar MA, Nassiri-Kashani M, Malakafzali B, Nikbin B, Khamesipour A. Plasma sCD26 and sCD30 levels in cutaneous Leishmaniasis. Acta tropica 2009;109: 61-63.
21. Jafari-Shakib R, Ajdary S, Mohtasham Amiri Z, Miramin Mohammadi A, Nourijelyani K, Mortazavi H, et al. CD26 expression on CD4+ T cells in patients with cutaneous Leishmaniasis. Clin Exp Immunol 2008; 153: 31-36.
22. Tolouei S, Ghaedi K, Khamesipour A, Akbari M, Baghaei M, Hasheminia SJ, et al. IL-23 and IL-27 levels in macrophages collected from peripheral blood of patients with healing vs non-healing form of cutaneous leishmaniasis. Iran J Parasitol 2012; 7:18-25.
23. Ajdary S, Jafari-Shakib R, Riazi-Rad F, Khamesipour A. Soluble CD26 and CD30 levels in patients with anthroponotic cutaneous leishmaniasis. J Infect 2007; 55:75-78.
24. Schwarz T, Remer KA, Nahrendorf W, Masic A, Siewe L, Müller W, et al. T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine. PLoS Pathog 2013; 9(6):e1003476.
25. Anderson CF, Lira R, Kamhawi S, Belkaid Y, Wynn TA, Sacks D. Il-10 and TGF-β control the establishment of persistent and transmissible infections produced by leishmania tropica in C57BL/6 mice. J Immunol 2008; 180: 4090-4097.
26. Belkaid Y, Hoffmann KF, Mendez S, Kamhawi S, Udey MC, Wynn TA, et al. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J Exp Med 2001; 194:1497-1506.
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IssueVol 12 No 3 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v12i3.3243
Keywords
Cutaneous leishmaniasis; Soluble Leishmania antigen (SLA); Immune response; Interferon gamma (IFNγ); Interleukin 10 (IL-10); Interleukin 5 (IL-5)

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How to Cite
1.
Miramin-Mohammadi A, Javadi A, Eskandari SE, Mortazavi H, Nateghi Rostami M, Khamesipour A. Immune response in cutaneous leishmaniasis patients with healing vs. non-healing lesions. Iran J Microbiol. 2020;12(3):249-255.