Immune Responses in Cutaneous Leishmaniasis: in vitro Thelper1/Thelper2 Cy-tokine Profiles Using Live Versus Killed Leishmania major
-
Akram Miramin-Mohammadi
,
Amir Javadi
,
Seyyed Ebrahim Eskandari
,
Mahmood Nateghi-Rostami
,
Ali Khamesipour
Abstract
Background: Recovery from cutaneous leishmaniasis (CL) leads to protection against further lesion development. In contrast, vaccination using killed parasites does not induce enough protection; the reason(s) is not currently known but might be related to different immune response induced against live versus killed parasites. In this study, Th1/Th2 cyto-kine profiles of CL patients were evaluated against live versus killed Leishmania major.
Methods: In this study peripheral blood mononuclear cells (PBMC) of the volunteers with active CL lesion (CL), history of CL (HCL) and healthy volunteers were cultured and stimulated with live or killed Leishmania major, the superna-tants were collected and levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method.
Results: The results showed that IFN-γ levels in CL patients (p< 0.001) and HCL volunteers (p< 0.005) are signifi-cantly higher when stimulated with live than stimulated with killed L. major. IFN-γ production in PBMC volunteers with CL and HCL stimulated with live or heat-killed L. major was significantly (p< 0.001) higher than in unstimulated ones. The level of IL-5 in CL patients (p< 0.005) and HCL volunteers (p< 0.001) are significantly lower when stimulated with live than killed L. major. There was no significant difference between the levels of IL-10 in PBMC stimulated with either live or killed L. major.
Conclusion: It is concluded that using live Leishmania induces a stronger Th1 type of immune response which justify using leishmanization as a control measure against CL.
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11. Ajdary S, Alimohammadian MH, Eslami MB, Kemp K, Kharazmi A (2000) Com-parison of the immune profile of non-healing cutaneous leishmaniasis patients with those with active lesions and those who have recovered from infection. In-fect Immun. 68(4): 1760–1764.
12. Rostami MN, Keshavarz H, Edalat R, Sar-rafnejad A, Shahrestani T, Mahboudi F (2010) CD8+ T cells as a source of IFN-γ production in human cutaneous leish-maniasis. Plos Neg Trop Dis. 4(10): e845.
13. Taheri AR, Goyonlo VM, Nahidi Y, Moheghi N, Afshari JT (2014) Plasma levels of interlukin-4 and interferon-γ in patients with chronic or healed cutane-ous leishmaniasis. Iran J Basic Med Sci. 17(3): 216–219.
14. Mohebali M, Nadim A, Khamesipour A (2019) An overview of leishmanization experience: A successful control meas-ure and a tool to evaluate candidate vac-cines. Acta Trop. 200: 105173.
15. Mahmoodi M, Rajabalian S, Fekri A, Esfiar-pour I (2005) Evaluation of in vitro pro-duction of IFN-γ, IL-10, IL-12 and IL-13 by blood cells in patients with cuta¬neous leishmaniasis lesions. Iran J Aller¬gy Asthma Immunol. 4(1): 15–22.
16. Overath P, Aebischer T (1999) Antigen presen¬tation by macrophages harboring intravesicular pathogens. Parasitol Today. 15(8): 325–332.
17. Belkaid Y, Piccirillo CA, Mendez S, She-vach EM, Sacks DL (2002) CD4+ CD 25+ regulatory T cells control Leishma-nia major persistence and immunity. Na-ture. 420(6915): 502–507.
18. Mendez S, Reckling SK, Piccirillo CA, Sacks D, Belkaid Y (2004) Role for CD4+ CD25+ regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med. 200 (2): 201–210.
19. Uzonna JE, Wei G, Yurkowski D, Bretscher P (2001) Immune elimination of Leish-mania major in mice: implications for im¬mune memory, vaccination, and reactiva¬tion disease. J Immunol. 167(12): 6967–6974.
20. Uzonna JE, Joyce KL, Scott P (2004) Low dose Leishmania major promotes a tran-sient T helper cell type 2 response that is down-regulated by interferon γ–producing CD8+ T cells. J Exp Med. 199(11): 1559–1566.
21. Nylen S, Mörtberg U, Kovalenko D, Satti I, Engström K, Bakhiet M (2001) Dif-ferential induction of cellular responses by live and dead Leishmania promastigotes in healthy donors. Clin Exp Immunol. 124 (1): 43–53.
22. Palatnik-de-Sousa CB (2008) Vaccines for leishmaniasis in the fore coming 25 years. Vaccine. 26(14): 1709–1724.
23. Sharifi I, FeKri AR, Aflatonian MR, Khamesipour A, Nadim A, Mousavi M-RA ( 1998) Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutane-ous leishmaniasis in Bam, Iran. Lancet. 351(9115): 1540–1543.
24. Khalil E, Hassan A, Zijlstra E, Mukhtar M, Ghalib H, Musa B (2000) Autoclaved Leish¬mania major vaccine for preven¬tion of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan. Lancet. 356(9241): 1565–1569.
25. Nylen S, Maasho K, Söderström K, Ilg T, Akuffo H (2003) Live Leishmania pro-mastigotes can directly activate primary human natural killer cells to produce in-terferon‐gamma. Clin Exp Immunol. 131 (3): 457–467.
26. Okwor I, Liu D, Uzonna J (2009) Qual-itative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strat-egies against Leishmaniasis. Vaccine. 27 (19): 2554–2562.
2. Hotez PJ, Bottazzi ME, Strych U (2016) New vaccines for the world's poorest people. Annu Rev Med. 67: 405–417.
3. Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J (2012) Leishmaniasis worldwide and global estimates of its incidence. PloS One. 7(5).
4. Murray H, Rubin B, Rothermel C (1983) Killing of intracellular Leishmania do-novani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lym-phokine. J Clin Invest. 72(4): 1506–1510.
5. Mosmann TR, Coffman R (1989) TH1 and TH2 cells: different patterns of lympho-kine secretion lead to different functional properties. Annu Rev Immunol. 7(1): 145–173.
6. Moafi M, Rezvan H, Sherkat R, Taleban R, Asilian A, Hamid Zarkesh‐Esfahani S, Nil¬foroushzadeh MA, Jaffary F, Mansouri-an M, Sokhanvari F, Ansari N (2017) Com¬parison of proinflammatory cyto-kines of non‐healing and healing cuta-neous leishmaniasis. Scand J Im-munol. 85(4): 291–299.
7. Mahmoodi M, Rajabalian S, Fekri A, Esfiar-pour I (2005) Evaluation of in vitro pro-duction of IFN-γ, IL-10, IL-12 and IL-13 by blood cells in patients with cuta¬neous leishmaniasis lesions. Iran J Aller¬gy Asthma Immunol. 4(1): 15–22.
8. Hejazi S, Hoseini S, Javanmard S, Zarkesh S, Khamesipour A (2012) Interleukin-10 and transforming growth factor-β in ear-ly and late lesions of patients with Leish¬mania major induced cutaneous leishman¬iasis. Iran J Parasitol. 7(2): 53–60.
9. Shahi M, Mohajery M, Shamsian SAA, Nahrevanian H, Yazdanpanah SMJ (2013) Comparison of Th1 and Th2 re-sponses in non-healing and healing patients with cutaneous leishmaniasis. Rep Biochem Mol Biol. 1(2): 43–48.
10. Habibi GR, Khamesipour A, McMaster W, Mahboudi F (2001) Cytokine gene ex-pression in healing and non‐healing cas-es of cutaneous leishmaniasis in re-sponse to in vitro stimulation with re-combinant gp63 using semiquantitative RT–PCR. Scand J Immunol. 54(4): 414–420.
11. Ajdary S, Alimohammadian MH, Eslami MB, Kemp K, Kharazmi A (2000) Com-parison of the immune profile of non-healing cutaneous leishmaniasis patients with those with active lesions and those who have recovered from infection. In-fect Immun. 68(4): 1760–1764.
12. Rostami MN, Keshavarz H, Edalat R, Sar-rafnejad A, Shahrestani T, Mahboudi F (2010) CD8+ T cells as a source of IFN-γ production in human cutaneous leish-maniasis. Plos Neg Trop Dis. 4(10): e845.
13. Taheri AR, Goyonlo VM, Nahidi Y, Moheghi N, Afshari JT (2014) Plasma levels of interlukin-4 and interferon-γ in patients with chronic or healed cutane-ous leishmaniasis. Iran J Basic Med Sci. 17(3): 216–219.
14. Mohebali M, Nadim A, Khamesipour A (2019) An overview of leishmanization experience: A successful control meas-ure and a tool to evaluate candidate vac-cines. Acta Trop. 200: 105173.
15. Mahmoodi M, Rajabalian S, Fekri A, Esfiar-pour I (2005) Evaluation of in vitro pro-duction of IFN-γ, IL-10, IL-12 and IL-13 by blood cells in patients with cuta¬neous leishmaniasis lesions. Iran J Aller¬gy Asthma Immunol. 4(1): 15–22.
16. Overath P, Aebischer T (1999) Antigen presen¬tation by macrophages harboring intravesicular pathogens. Parasitol Today. 15(8): 325–332.
17. Belkaid Y, Piccirillo CA, Mendez S, She-vach EM, Sacks DL (2002) CD4+ CD 25+ regulatory T cells control Leishma-nia major persistence and immunity. Na-ture. 420(6915): 502–507.
18. Mendez S, Reckling SK, Piccirillo CA, Sacks D, Belkaid Y (2004) Role for CD4+ CD25+ regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med. 200 (2): 201–210.
19. Uzonna JE, Wei G, Yurkowski D, Bretscher P (2001) Immune elimination of Leish-mania major in mice: implications for im¬mune memory, vaccination, and reactiva¬tion disease. J Immunol. 167(12): 6967–6974.
20. Uzonna JE, Joyce KL, Scott P (2004) Low dose Leishmania major promotes a tran-sient T helper cell type 2 response that is down-regulated by interferon γ–producing CD8+ T cells. J Exp Med. 199(11): 1559–1566.
21. Nylen S, Mörtberg U, Kovalenko D, Satti I, Engström K, Bakhiet M (2001) Dif-ferential induction of cellular responses by live and dead Leishmania promastigotes in healthy donors. Clin Exp Immunol. 124 (1): 43–53.
22. Palatnik-de-Sousa CB (2008) Vaccines for leishmaniasis in the fore coming 25 years. Vaccine. 26(14): 1709–1724.
23. Sharifi I, FeKri AR, Aflatonian MR, Khamesipour A, Nadim A, Mousavi M-RA ( 1998) Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutane-ous leishmaniasis in Bam, Iran. Lancet. 351(9115): 1540–1543.
24. Khalil E, Hassan A, Zijlstra E, Mukhtar M, Ghalib H, Musa B (2000) Autoclaved Leish¬mania major vaccine for preven¬tion of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan. Lancet. 356(9241): 1565–1569.
25. Nylen S, Maasho K, Söderström K, Ilg T, Akuffo H (2003) Live Leishmania pro-mastigotes can directly activate primary human natural killer cells to produce in-terferon‐gamma. Clin Exp Immunol. 131 (3): 457–467.
26. Okwor I, Liu D, Uzonna J (2009) Qual-itative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strat-egies against Leishmaniasis. Vaccine. 27 (19): 2554–2562.
| Files | ||
| Issue | Vol 15 No 1 (2021) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/jad.v15i1.6491 | |
| Keywords | ||
| Cutaneous leishmaniasis; Live Leishmania; Heat-killed Leishmania; In vitro Immune response | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Miramin-Mohammadi A, Javadi A, Eskandari SE, Nateghi-Rostami M, Khamesipour A. Immune Responses in Cutaneous Leishmaniasis: in vitro Thelper1/Thelper2 Cy-tokine Profiles Using Live Versus Killed Leishmania major. J Arthropod Borne Dis. 2021;15(1):126-135.
