M. Güran, An Overview of Leishmaniasis: Historic to Future Perspectives, Vectors and Vector-Borne 480 Zoonotic Diseases, 2018.

P. S. Veras, P. I. Ramos, and J. P. De-menezes, In search of biomarkers for pathogenesis and control of 482 leishmaniasis by global analyses of Leishmania-infected macrophages, Frontiers in Cellular and Infection, vol.483, 2018.

E. Ontoria, Y. E. Hernández-santana, A. C. González-garcía, M. C. Lopez, B. Valladares et al., 485 Transcriptional profiling of immune-related genes in Leishmania infantum-infected mice: identification 486 of potential biomarkers of infection and progression of disease, Frontiers in cellular and infection, vol.487, issue.8, p.197, 2018.

E. R. Mears, F. Modabber, R. Don, and G. E. Johnson, A review: The current in vivo models for the 489 discovery and utility of new anti-leishmanial drugs targeting cutaneous leishmaniasis, PLoS neglected 490 tropical diseases, vol.9, p.3889, 2015.

D. J. Matthews, C. L. Emson, G. J. Mckenzie, H. E. Jolin, J. M. Blackwell et al., IL-13 is a 492 susceptibility factor for Leishmania major infection, The Journal of Immunology, vol.164, issue.3, pp.1458-493, 2000.

R. Chatelain, S. Mauze, and R. L. Coffman, Experimental Leishmania major infection in mice: role of IL-10, Parasite immunology, vol.495, issue.4, pp.211-218, 1999.

Y. Li, K. Ishii, H. Hisaeda, S. Hamano, M. Zhang et al.,

. Akira, IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c 498 mice: is the effect mediated by the CpG signaling TLR9?, Gene therapy, vol.11, issue.11, p.941, 2004.

W. Kammoun-rebai, I. Naouar, V. Libri, M. Albert, H. Louzir et al., Protein 500 biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for 501 cutaneous leishmaniasis, BMC infectious diseases, vol.16, issue.1, p.138, 2016.

M. Jabbour, G. Issa, K. Charafeddine, Y. Simaan, M. Karam et al., The 503 immune microenvironment in cutaneous leishmaniasis, Journal of the European Academy of 504 Dermatology and Venereology, vol.29, issue.6, 2015.

S. M. Christensen, L. A. Dillon, L. P. Carvalho, S. Passos, F. O. Novais et al., , p.506

P. Carvalho, N. M. Scott, and . El-sayed, Meta-transcriptome profiling of the human-Leishmania braziliensis 507 cutaneous lesion, PLoS neglected tropical diseases, vol.10, issue.9, p.4992, 2016.

F. Bahrami, A. M. Harandi, and S. Rafati, Biomarkers of Cutaneous Leishmaniasis, Frontiers in cellular and 509 infection microbiology, vol.8, p.222, 2018.

R. Kumar, R. A. Bumb, and P. Salotra, Correlation of parasitic load with interleukin-4 response in patients 511 with cutaneous leishmaniasis due to Leishmania tropica, FEMS Immunology & Medical Microbiology, vol.512, issue.3, pp.239-246, 2009.

R. Kumar, R. A. Bumb, and P. Salotra, Evaluation of localized and systemic immune responses in 514 cutaneous leishmaniasis caused by Leishmania tropica: interleukin-8, monocyte chemotactic protein-1 515 and nitric oxide are major regulatory factors, Immunology, vol.130, issue.2, pp.193-201, 2010.

N. B. Norsworthy, J. Sun, D. Elnaiem, G. Lanzaro, and L. Soong, Sand fly saliva enhances Leishmania 517 amazonensis infection by modulating interleukin-10 production, Infection and immunity, vol.72, issue.3, pp.1240-1247, 2004.

K. E. Iles and H. J. Forman, Macrophage signaling and respiratory burst, Immunologic research, vol.26, issue.1-3, pp.95-105, 2002.

R. Tibúrcio, S. Nunes, I. Nunes, M. R. Ampuero, I. B. Silva et al., , p.522

, Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View, Frontiers in 523 immunology, vol.10, 2019.

M. Shahi, M. Mohajery, S. A. Shamsian, H. Nahrevanian, and S. M. Yazdanpanah, Comparison of Th1 525 and Th2 responses in non-healing and healing patients with cutaneous leishmaniasis, Reports of 526 biochemistry & molecular biology, vol.1, issue.2, p.43, 2013.

M. Rossi and N. Fasel, How to master the host immune system? Leishmania parasites have the 528 solutions!, International immunology, vol.30, issue.3, pp.103-111, 2017.

Y. Taslimi, P. Sadeghipour, S. Habibzadeh, V. Mashayekhi, H. Mortazavi et al.,

S. Kropf and . Rafati, A novel non-invasive diagnostic sampling technique for cutaneous leishmaniasis, PLoS 531 neglected tropical diseases, vol.11, p.5750, 2017.

Y. Taslimi and S. Rafati, Possible Diagnostic Improvement for Cutaneous Leishmaniasis: Is It 533 Achievable?, Iranian biomedical journal, vol.22, issue.4, pp.215-216, 2018.

M. Lundberg, A. Eriksson, B. Tran, E. Assarsson, and S. Fredriksson, Homogeneous antibody-based 535 proximity extension assays provide sensitive and specific detection of low-abundant proteins in human 536 blood, Nucleic acids research, vol.39, issue.15, pp.102-102, 2011.

E. Assarsson, M. Lundberg, G. Holmquist, J. Björkesten, S. B. Thorsen et al.,

S. Dickens, G. Ohlsson, and . Edfeldt, Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, 539 specificity, and excellent scalability, PloS one, vol.9, issue.4, p.95192, 2014.

S. A. Ejazi, P. Bhattacharya, M. A. Bakhteyar, A. A. Mumtaz, K. Pandey et al., , p.541

R. P. Rahaman, N. Goswami, and . Ali, Noninvasive diagnosis of visceral leishmaniasis: development and 542 evaluation of two urine-based immunoassays for detection of Leishmania donovani Infection in India, PLoS neglected tropical diseases, vol.543, issue.10, p.5035, 2016.

M. Krzywinski, J. Schein, I. Birol, J. Connors, R. Gascoyne et al., Circos: 545 an information aesthetic for comparative genomics, Genome research, vol.19, issue.9, pp.1639-1645, 2009.

M. Martínez-lópez, M. Soto, S. Iborra, and D. Sancho, Leishmania hijacks myeloid cells for immune 547 escape, Frontiers in microbiology, vol.9, p.883, 2018.

S. Oghumu, C. M. Lezama-dávila, A. P. Isaac-márquez, and A. R. Satoskar, Role of chemokines in 549 regulation of immunity against leishmaniasis, Experimental parasitology, vol.126, issue.3, pp.389-396, 2010.

S. M. Christensen, A. T. Belew, N. M. El-sayed, W. L. Tafuri, F. T. Silveira et al., Host and 551 parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis, PLoS neglected 552 tropical diseases, vol.13, p.7152, 2019.

D. Menezes-souza, R. Guerra-sá, C. M. Carneiro, J. Vitoriano-souza, and R. C. Giunchetti,

D. Carvalho, G. C. Silveira-lemos, R. Oliveira, A. B. Corrêa-oliveira, and . Reis, Higher expression of CCL2, vol.4, p.555

, CCL5, CCL21, and CXCL8 chemokines in the skin associated with parasite density in canine visceral 556 leishmaniasis, vol.6, p.1566, 2012.

A. Coondoo, The role of cytokines in the pathomechanism of cutaneous disorders, Indian journal of 558 dermatology, vol.57, issue.2, p.90, 2012.

N. Maspi, A. Abdoli, and F. Ghaffarifar, Pro-and anti-inflammatory cytokines in cutaneous leishmaniasis: 560 a review, Pathogens and global health, vol.110, issue.6, pp.247-260, 2016.

K. Ohkusu, T. Yoshimoto, K. Takeda, T. Ogura, S. Kashiwamura et al.,

. Nakanishi, Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania 563 major infection, Infection and immunity, vol.68, issue.5, pp.2449-2456, 2000.

C. D. Richards, The enigmatic cytokine oncostatin m and roles in disease, ISRN inflammation, p.565, 2013.

M. Jaramillo, M. A. Gomez, O. Larsson, M. T. Shio, I. Topisirovic et al.,

R. Rosenfeld, R. W. Colina, and . Mcmaster, Leishmania repression of host translation through mTOR cleavage 568 is required for parasite survival and infection, Cell host & microbe, vol.9, issue.4, pp.331-341, 2011.

C. S. Subauste, CD40 and the immune response to parasitic infections, Seminars in immunology, p.570

B. Babai, H. Louzir, P. Cazenave, and K. Dellagi, Depletion of peritoneal CD5+ B cells has no effect on 572 the course of Leishmania major infection in susceptible and resistant mice, Clinical and experimental 573 immunology, vol.117, issue.1, p.123, 1999.

M. J. Sweet and D. A. Hume, CSF-1 as a regulator of macrophage activation and immune responses, p.575

, ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS-ENGLISH EDITION, vol.51, issue.3, pp.169-178, 2003.

T. Weinkopff, C. Konradt, D. A. Christian, D. E. Discher, C. A. Hunter et al., Leishmania major 577 Infection-Induced VEGF-A/VEGFR-2 Signaling Promotes Lymphangiogenesis That Controls Disease, The 578 Journal of Immunology, vol.197, issue.5, pp.1823-1831, 2016.

R. Herro, R. D. Antunes, A. R. Aguilera, K. Tamada, and M. Croft, The tumor necrosis factor superfamily 580 molecule LIGHT promotes keratinocyte activity and skin fibrosis, Journal of Investigative Dermatology, vol.581, issue.8, pp.2109-2118, 2015.

A. C. Stanley, F. De-labastida-rivera, A. Haque, M. Sheel, Y. Zhou et al.,

K. Randall, S. Pfeffer, and . Scheu, Critical roles for LIGHT and its receptors in generating T cell-mediated 584 immunity during Leishmania donovani infection, PLoS pathogens, vol.7, issue.10, p.1002279, 2011.

L. Almeida, J. A. Silva, V. M. Andrade, P. Machado, S. E. Jamieson et al., , p.586

. Castellucci, Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by 587

, Leishmania braziliensis infection, vol.49, pp.212-220, 2017.

F. Souza-silva, S. C. Bourguignon, B. A. Pereira, L. M. De-castro-côrtes, and L. F. De-oliveira,

L. C. Henriques-pons, V. F. Finkelstein, P. F. Ferreira, R. T. Carneiro, and . De-pinho, Epoxy-?-lapachone has in 590 vitro and in vivo anti-leishmania (Leishmania) amazonensis effects and inhibits serine proteinase activity 591 in this parasite, Antimicrobial agents and chemotherapy, vol.59, issue.4, pp.1910-1918, 2015.

G. Tasew, S. Nylén, T. Lieke, B. Lemu, H. Meless et al.,

. Britton, Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration, PLoS 594 neglected tropical diseases, vol.4, p.844, 2010.

W. F. Pereira-manfro, F. L. Ribeiro-gomes, A. A. Filardy, N. S. Vellozo, L. V. Guillermo et al., , p.596

G. A. Siegel, M. F. Dosreis, and . Lopes, Inhibition of caspase-8 activity promotes protective Th1-and 597

, Th2-mediated immunity to Leishmania major infection, Journal of leukocyte biology, vol.95, issue.2, pp.347-598, 2014.

K. R. Gantt, S. Schultz-cherry, N. Rodriguez, S. M. Jeronimo, E. T. Nascimento et al., , p.600

M. A. Recker, M. E. Miller, and . Wilson, Activation of TGF-? by Leishmania chagasi: importance for parasite 601 survival in macrophages, The Journal of Immunology, vol.170, issue.5, pp.2613-2620, 2003.

S. Jurcevic, K. Klinga-levan, B. Olsson, and K. Ejeskär, Verification of microRNA expression in human 603 endometrial adenocarcinoma, BMC cancer, vol.16, issue.1, p.261, 2016.

J. Meephansan, U. Subpayasarn, M. Komine, and M. Ohtsuki, Pathogenic role of cytokines and effect of 605 their inhibition in psoriasis, Psoriasis: An Interdisciplinary Approach, p.41, 2017.

S. C. Liang, R. J. Greenwald, Y. E. Latchman, L. Rosas, A. Satoskar et al., PD-L1 607 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis, European journal 608 of immunology, vol.36, issue.1, pp.58-64, 2006.

, We confirm that the manuscript was approved by all authors and the authors declare no conflict of interest, and that the results presented in this manuscript have neither been published nor under consideration for publication elsewhere

, *Declaration of Interest Statement