Articles

Interleukin-10 and Transforming Growth Factor-β in Early and Late Lesions of Patients with Leishmania major Induced Cutane­ous Leishmaniasis

Abstract

Background: Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL)-10 and transforming growth factor (TGF)-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-β in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-β in human cutaneous leishmaniasis due to Leishmania major infection.

Methods: Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-β positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions.

Results: The mean percentage of IL-10 positive cells were significantly (P= 0.035) higher in late lesions (0.51±0.24) than early ones (0.15±0.07). Similar results were obtained for TGF-β with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008).

Conclusion: IL-10 and TGF-β are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.

Dowlati Y. Cutaneous leishmaniasis: clinicalaspect. Clin Dermatol. 1996; 14(5):425-31.

Desjeux P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis. 2004 Sep;27(5):305-18.

Dowlati Y. Treatment of cutaneous leishmaniasis (Old World). Clin Dermatol. 1996; 14(5):513-7.

Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002;2:845-58.

Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature. 2002;420(6915):502-7.

Xu DLH, Komai-Koma M, Campbell C, McSharry C, Alexander J, Liew FY. CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, Leishmania major infection, and colitis in mice. J Immunol. 2003;170:394-9.

Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factorbeta regulation of immune responses. Annu Rev Immunol. 2006;24:99-146.

Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010(5):331-44.

Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3(1):23-35.

Shalev I, Schmelzle M, Robson SC, Levy G. Making sense of regulatory T cell suppressive function. Semin Immunol. 2011; 23(4):282-92.

Melby PC, Andrade-Narvaez FJ, Darnell BJ, Valencia-Pacheco G, Tryon VV, Palomo- Cetina A. Increased expression of proinflammatory cytokines in chronic lesions of human cutaneous leishmaniasis. Infect Immun. 1994;62(3):837-42.

Diaz NL, Zerpa O, Ponce LV, Convit J, Rondon AJ, Tapia FJ. Intermediate or chronic cutaneous leishmaniasis: leukocyte immunophenotypes and cytokine characterisation of the lesion. Exp Dermatol. 2002;11(1):34-41.

Nasereddin A, Jaffe CL. Rapid diagnosis of Old World Leishmaniasis by high-resolution melting analysis of the 7SL RNA gene. J Clin Microbiol. 2010;48(6):2240-2.

Kane MM, Mosser DM. The role of IL-10 in promoting disease progression in leishmaniasis. J Immunol. 2001 15; 166(2):1141-7.

Groux H, Cottrez F, Rouleau M, Mauze S, Antonenko S, Hurst S, et al. A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. J Immunol. 1999;162(3):1723-9.

Viana da Costa A, Huerre M, Delacre M, Auriault C, Correia Costa JM, Verwaerde C. IL-10 leads to a higher parasite persistencem in a resistant mouse model of Leishmania major infection. Parasitol Int. 2002; 51(4):367-79.

Belkaid Y. 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;194:1497-506.

Louzir H, Melby PC, Ben Salah A, Marrakchi H, Aoun K, Ben Ismail R, et al. Immunologic determinants of disease evolution in localized cutaneous leishmaniasis, due to Leishmania major. J Infect Dis.m1998;177(6):1687-95.

Bourreau E, Prevot G, Gardon J, Pradinaud, Launois P. High intralesional interleukin-10 messenger RNA expression in localized cutaneous leishmaniasis is associated with unresponsiveness to treatment. J Infect Dis. 2001;184(12):1628-30.

Bourreau E, Ronet C, Darcissac E, Lise MC, Sainte Marie D, Clity E, et al. Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect Immun. 2009;77(4):1465-74.

Gaafar A, Veress B, Permin H, Kharazmi A, Theander TG, el Hassan AM. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major. Clin Immunol. 1999;91(3):314-20.

Machado PR, Rosa ME, Costa D, Mignac M, Silva JS, Schriefer A, et al. Reappraisal of the immunopathogenesis of disseminated leishmaniasis: in situ and systemic immune response. Trans R Soc Trop Med Hyg. 2011;105(8):438-44.

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(4):1760-4.

Habibi GR, Khamesipour A, McMaster WR, Mahboudi F. Cytokine gene expression in healing and non-healing cases of cutaneous leishmaniasis in response to in vitro stimulation with recombinant gp63 using semiquantitative RT-PCR. Scand J Immunol. 2001;54(4):414-20.

Jafari-Shakib R, Ajdary S, Amiri ZM, Mohammadi AM, Nourijelyani K, Mortazavi H, et al. CD26 expression on CD4+T cells in patients with cutaneous leishmaniasis.Clin Exp Immunol. 2008;153(1):31-6.

Nilsen R, Mshana RN. In situ characterization of the cutaneous immune response in Ethiopian cutaneous leishmaniasis. Scand J Immunol. 1987;26(5):503-12.

Enk AH, Katz SI. Identification and induction of keratinocyte-derived IL-10. J Immunol. 1992;149(1):92-5.

O'Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol. 2007;7(6):425-8.

O'Garra A, Vieira PL, Vieira P, Goldfeld AE. IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage. J Clin Invest. 2004;114:1372-8.

Anderson CF, Oukka M, Kuchroo VJ, Sacks D. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med. 2007; 204(2):285-97.

Suffia IJ, Reckling SK, Piccirillo CA, Goldszmid RS, Belkaid Y. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J Exp Med. 2006;203(3):777-88.

Reed SG. TGF-beta in infections and infectious diseases. Microbes Infect. 1999; 1(15):1313-25.

Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci. 2003;116(Pt 2):217-24.

Ferguson MW, O'Kane S. Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc

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IssueVol 7 No 3 (2012) QRcode
SectionArticles
Keywords
Cutaneous leishmaniasis Leishmania major Interleukin-10 Transforming growth factor-β Immunofluorescence

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How to Cite
1.
Hejazi S, Hoseini S, Javanmard S, Zarkesh S, Khamesipour A. Interleukin-10 and Transforming Growth Factor-β in Early and Late Lesions of Patients with Leishmania major Induced Cutane­ous Leishmaniasis. Iran J Parasitol. 1;7(3):16-23.