Leishmania pp 315-349 | Cite as

Experimental Cutaneous Leishmaniasis: Mouse Models for Resolution of Inflammation Versus Chronicity of Disease

  • Christian BogdanEmail author
  • Andrea Debus
  • Heidi Sebald
  • Baplu Rai
  • Johanna Schäfer
  • Stephanie Obermeyer
  • Ulrike Schleicher
Part of the Methods in Molecular Biology book series (MIMB, volume 1971)


Experimental cutaneous leishmaniasis of mice is a valuable model to study the immune response to the protozoan pathogen Leishmania and to define mechanisms of parasite control and resolution of inflammation as well as of parasite evasion and chronicity of disease. In addition, over many years Leishmania-infected mice have been successfully used to analyze the function of newly discovered immune cell types, transcription factors, cytokines, and effector mechanisms in vivo. In this chapter we present detailed protocols for the culture, propagation, and inoculation of Leishmania promastigotes, the monitoring of the course of cutaneous infection, the determination of the tissue parasite burden and for the phenotyping of the ensuing immune response. The focus lies on the L. major mouse model, but an overview on other established models of murine cutaneous leishmaniasis is also provided.

Key words

Leishmania major Mouse models Cutaneous leishmaniasis 



The preparation of the manuscript and some of the studies reviewed were supported by the Deutsche Forschungsgemeinschaft (SFB1181, project C4; GK1660, project A5; SPP1937, Bo996/5-1), the Interdisciplinary Center for Clinical Research (IZKF) of the Universitätsklinikum Erlangen (project A61 and A63), and the Bundesministerium für Bildung und Forschung (BMBF; Infect-Era “EpiCross”).


  1. 1.
    Rittig MC, Bogdan C (2000) Leishmania-host cell interaction: complexities and alternative views. Parasitol Today 16:292–297PubMedCrossRefGoogle Scholar
  2. 2.
    Kaye P, Scott P (2011) Leishmaniasis: complexity at the host-pathogen interface. Nat Rev Microbiol 9(8):604–615PubMedCrossRefGoogle Scholar
  3. 3.
    Bogdan C (2012) Leishmaniasis in rheumatology, hematology, and oncology: epidemiological, immunological, and clinical aspects and caveats. Ann Rheum Dis 71(suppl 2):i60–i66PubMedCrossRefGoogle Scholar
  4. 4.
    Banuls AL, Bastien P, Pomares C, Arevalo J, Fisa R, Hide M (2011) Clinical pleiomorphism in human leishmaniases, with special mention of asymptomatic infection. Clin Microbiol Infect 17(10):1451–1461PubMedCrossRefGoogle Scholar
  5. 5.
    Leishmaniasis: worldwide epidemiological and drug access update (2012) WHO. Accessed May 30 2012
  6. 6.
    Steverding D (2017) The history of leishmaniasis. Parasit Vectors 10(1):82. Scholar
  7. 7.
    Bayon H (1912) Demonstration of specimens relating to the transmission of artificial cultures of Leishmania infantum to mice and rats. Brit Med J 2(2705):1197–1199Google Scholar
  8. 8.
    Philippe E, Chadli A (1961) Experimental leishmaniasis in the mouse (Leishmania donovani and Leishmania tropica). Arch Inst Pasteur Tunis 38:241–254PubMedGoogle Scholar
  9. 9.
    Kellina OI (1973) Differences of susceptibility of inbred mice of different strains to Leishmania tropica major. Med Parazitol Parazit Bolezni 42:279Google Scholar
  10. 10.
    Handman E, Ceredig R, Mitchell GF (1979) Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Aust J Exp Biol Med Sci 57:9–29PubMedCrossRefGoogle Scholar
  11. 11.
    Howard JG, Hale C, Chan-Liew WL (1980) Immunological regulation of experimental cutaneous leishmaniasis. I. Immunogenetic aspects of susceptibility to Leishmania tropica in mice. Parasite Immunol 2:303–314PubMedCrossRefGoogle Scholar
  12. 12.
    DeTolla LJ, Scott PA, Farrell JP (1981) Single gene control of resistance to cutaneous leishmaniasis in mice. Immunogenetics 14(1–2):29–39PubMedCrossRefGoogle Scholar
  13. 13.
    Preston PM, Carter RL, Leuchars E, Davies AJS, Dumonde DC (1972) Experimental cutaneous leishmaniasis. III. Effects of thymectomy on the course of infection of CBA mice with Leishmania tropica. Clin Exp Immunol 10:337–344PubMedPubMedCentralGoogle Scholar
  14. 14.
    Leclerc C, Modabber F, Deriaud E, Cheddid L (1981) Systemic infection of Leishmania tropica (major) in various strains of mice. Trans R Soc Trop Med Hyg 75:851–854PubMedCrossRefGoogle Scholar
  15. 15.
    Nasseri M, Modabber FZ (1979) Generalized infection and lack of delayed hypersensitivity in BALB/c mice infected with Leishmania tropica major. Infect Immun 26(2):611–614PubMedPubMedCentralGoogle Scholar
  16. 16.
    Preston PM, Dumonde DC (1976) Experimental cutaneous leishmaniasis V. Protective immunity in subclinical and self-healing infection in the mouse. Clin Exp Immunol 23:126–138PubMedPubMedCentralGoogle Scholar
  17. 17.
    Preston PM (1973) Immunology in cutaneous leishmaniasis. Proc Roy Soc Med 66(8):776–777PubMedGoogle Scholar
  18. 18.
    Bretscher PA, Wei G, Menon JN, Bielefeldt-Ohmann H (1992) Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. Science 257:539–542PubMedCrossRefGoogle Scholar
  19. 19.
    Pérez H, Arredondo B, Gonzalez M (1978) Comparative study of American cutaneous leishmaniasis and diffuse cutaneous leishmaniasis in two strains of inbred mice. Infect Immun 22:301–307PubMedPubMedCentralGoogle Scholar
  20. 20.
    Courret N, Lang T, Milon G, Antoine JC (2003) Intradermal inoculations of low doses of Leishmania major and Leishmania amazonensis metacyclic promastigotes induce different immunoparasitic processes and status of protection in BALB/c mice. Int J Parasitol 33(12):1373–1383PubMedCrossRefGoogle Scholar
  21. 21.
    Lira R, Doherty M, Modi G, Sacks DL (2000) Evolution of lesion formation, parasitic load, immune response, and reservoir potential in C57BL/6 mice following high- and low-dose challenge with Leishmania major. Infect Immun 68:5176–5182PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    da Silva R, Sacks DL (1987) Metacyclogenesis is a major determinant of Leishmania promastigote virulence and attenuation. Infect Immun 55(11):2802–2806PubMedPubMedCentralGoogle Scholar
  23. 23.
    Lang T, Courret N, Colle JH, Milon G, Antoine JC (2003) The levels and patterns of cytokines produced by CD4 T lymphocytes of BALB/c mice infected with Leishmania major by inoculation into the ear dermis depend on the infectiousness and size of the inoculum. Infect Immun 71(5):2674–2683PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Felizardo TC, Toma LS, Borges NB, Lima GM, Abrahamsohn IA (2007) Leishmania (Leishmania) amazonensis infection and dissemination in mice inoculated with stationary-phase or with purified metacyclic promastigotes. Parasitology 134(Pt 12):1699–1707PubMedGoogle Scholar
  25. 25.
    van Zandbergen G, Bollinger A, Wenzel A, Kamhawi S, Voll R, Klinger M, Muller A, Holscher C, Herrmann M, Sacks D, Solbach W, Laskay T (2006) Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum. Proc Natl Acad Sci U S A 103(37):13837–13842PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Noben-Trauth N, Paul WE, Sacks DL (1999) IL-4- and IL-4 receptor-deficient BALB/c mice reveal differences in susceptibility to Leishmania major parasite substrains. J Immunol 162:6132–6140PubMedGoogle Scholar
  27. 27.
    Ritter U, Mattner J, Soares Rocha J, Bogdan C, Körner H (2004) The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain. Microbes Infect 6:559–565PubMedCrossRefGoogle Scholar
  28. 28.
    Anderson CF, Mendez S, Sacks DL (2005) Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57BL/6 mice. J Immunol 174:2934–2941PubMedCrossRefGoogle Scholar
  29. 29.
    Lee SH, Charmoy M, Romano A, Paun A, Chaves MM, Cope FO, Ralph DA, Sacks DL (2018) Mannose receptor high, M2 dermal macrophages mediate nonhealing Leishmania major infection in a Th1 immune environment. J Exp Med 215(1):357–375PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Indiani de Oliveira C, Teixeira MJ, Teixeira CR, Ramos de Jesus J, Bomura Rosato A, Santa da Silva J, Brodskyn C, Barral-Netto M, Barral A (2004) Leishmania braziliensis isolates differing at the genome level display distinctive features in BALB/c mice. Microbes Infect 6(11):977–984PubMedCrossRefGoogle Scholar
  31. 31.
    Teixeira MJ, Fernandes JD, Teixeira CR, Andrade BB, Pompeu ML, da Silva JS, Brodskyn CI, Barral-Netto M, Barral A (2005) Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns. Infect Immun 73:1191–1195PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Sulahian A, Garin YJ, Pratlong F, Dedet JP, Derouin F (1997) Experimental pathogenicity of viscerotropic and dermotropic isolates of Leishmania infantum from immunocompromised and immunocompetent patients in a murine model. FEMS Immunol Med Microbiol 17(3):131–138PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Garin YJ, Sulahian A, Pratlong F, Meneceur P, Gangneux JP, Prina E, Dedet JP, Derouin F (2001) Virulence of Leishmania infantum is expressed as a clonal and dominant phenotype in experimental infections. Infect Immun 69(12):7365–7373PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Nabors GS, Nolan T, Croop W, Li J, Farrell JP (1995) The influence of the site of parasite inoculation on the development of Th1 and Th2 type immune responses in (BALB/c x C57BL/6) F1 mice infected with Leishmania major. Parasite Immunol 17:569–579PubMedCrossRefGoogle Scholar
  35. 35.
    Kirkpatrick CE, Nolan TJ, Farrell JP (1987) Rate of Leishmania-induced skin-lesion development in rodents depends on the site of inoculation. Parasitology 94(Pt 3):451–465PubMedCrossRefGoogle Scholar
  36. 36.
    Baldwin TM, Elso C, Curtis J, Buckingham L, Handman E (2003) The site of Leishmania major infection determines disease severity and immune responses. Infect Immun 71(12):6830–6834PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Felizardo TC, Gaspar-Elsas MI, Lima GM, Abrahamsohn IA (2012) Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin--than on footpad-infected mice. Exp Parasitol 130(1):48–57PubMedCrossRefGoogle Scholar
  38. 38.
    Rosas LE, Keiser T, Barbi J, Satoskar AA, Septer A, Kaczmarek J, Lezama-Davila CM, Satoskar AR (2005) Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice. Int Immunol 17(10):1347–1357PubMedCrossRefGoogle Scholar
  39. 39.
    Mitchell GF, CJ M, Handman E (1981) Resistance to cutaneous leishmaniasis in genetically susceptible BALB/c mice. Aust J Exp Biol Med Sci 59:555–565PubMedCrossRefGoogle Scholar
  40. 40.
    Scott PA, Farrell JP (1982) Experimental cutaneous leishmaniasis: disseminated leishmaniasis in genetically susceptible and resistant mice. Am J Trop Med Hyg 31(2):230–238PubMedCrossRefGoogle Scholar
  41. 41.
    Melby PC, Yang Y-Z, Cheng J, Zhao W (1998) Regional differences in the cellular immune response to experimental cutaneous or visceral leishmaniasis with Leishmania donovani. Infect Immun 66:18–27PubMedPubMedCentralGoogle Scholar
  42. 42.
    Alexander J (1988) Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major. Parasitology 96(Pt 2):297–302PubMedCrossRefGoogle Scholar
  43. 43.
    Mock BA, Nacy CA (1988) Hormonal modulation of sex differences in resistance to Leishmania major systemic infections. Infect Immun 56(12):3316–3319PubMedPubMedCentralGoogle Scholar
  44. 44.
    Satoskar A, Alexander J (1995) Sex-determined susceptibility and differential IFN-γ and TNF-α mRNA expression in DBA/2 mice infected with Leishmania mexicana. Immunology 84:1–4PubMedPubMedCentralGoogle Scholar
  45. 45.
    Bryson KJ, Millington OR, Mokgethi T, McGachy HA, Brombacher F, Alexander J (2011) BALB/c mice deficient in CD4 T cell IL-4Ralpha expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype. PLoS Negl Trop Dis 5(1):e930. Scholar
  46. 46.
    Cillari E, Milano S, Dieli M, Arcoleo F, Perego R, Leoni F, Gromo G, Severn A, Liew FY (1992) Thymopentin reduces the susceptibility of aged mice to cutaneous leishmaniasis by modulating CD4 T-cell subsets. Immunol 76:362–366Google Scholar
  47. 47.
    Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, Belkaid Y, Chougnet C (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181(3):1835–1848PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Kropf P, Herath S, Weber V, Modolell M, Muller I (2003) Factors influencing Leishmania major infection in IL-4-deficient BALB/c mice. Parasite Immunol 25(8–9):439–447PubMedCrossRefGoogle Scholar
  49. 49.
    Quinonez-Diaz L, Mancilla-Ramirez J, Avila-Garcia M, Ortiz-Avalos J, Berron A, Gonzalez S, Paredes Y, Galindo-Sevilla N (2012) Effect of ambient temperature on the clinical manifestations of experimental diffuse cutaneous leishmaniasis in a rodent model. Vector Borne Zoonot Dis 12(10):851–860CrossRefGoogle Scholar
  50. 50.
    Sacks DL, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2:845–858CrossRefGoogle Scholar
  51. 51.
    Bogdan C (2008) Mechanisms and consequences of persistence of intracellular pathogens: leishmaniasis as an example. Cell Microbiol 10:1221–1234PubMedCrossRefGoogle Scholar
  52. 52.
    Bogdan C, Gessner A, Röllinghoff M (1993) Cytokines in Leishmaniasis: a complex network of stimulatory and inhibitory interactions. Immunobiology 189:356–396PubMedCrossRefGoogle Scholar
  53. 53.
    Bogdan C, Röllinghoff M (1998) The immune response to Leishmania: mechanisms of parasite control and evasion. Int J Parasitol 28:121–134PubMedCrossRefGoogle Scholar
  54. 54.
    Schleicher U, Paduch K, Debus A, Obermeyer S, Konig T, Kling JC, Ribechini E, Dudziak D, Mougiakakos D, Murray PJ, Ostuni R, Korner H, Bogdan C (2016) TNF-mediated restriction of arginase 1 expression in myeloid cells triggers type 2 no synthase activity at the site of infection. Cell Rep 15(5):1062–1075PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    McMahon-Pratt D, Alexander J (2004) Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunol Rev 201:206–224PubMedCrossRefGoogle Scholar
  56. 56.
    Stenger S, Thüring H, Röllinghoff M, Manning P, Bogdan C (1995) L-N6-(1-iminoethyl)lysine potently inhibits inducible nitric oxide synthase and is superior to NG-monomethyl-arginine in vitro and in vivo. Eur J Pharmacol 294:703–712PubMedCrossRefGoogle Scholar
  57. 57.
    Solbach W, Forberg K, Kammerer E, Bogdan C, Röllinghoff M (1986) Suppressive effect of cyclosporin A on the development of Leishmania tropica-induced lesions in genetically susceptible BALB/c mice. J Immunol 137:702–707PubMedGoogle Scholar
  58. 58.
    Solbach W, Forberg K, Röllinghoff M (1986) Effect of T-lymphocyte suppression on the parasite burden in Leishmania major-infected, genetically susceptible BALB/c mice. Infect Immun 54:909–912PubMedPubMedCentralGoogle Scholar
  59. 59.
    Unsoeld H, Mueller K, Schleicher U, Bogdan C, Zwirner J, Voehringer D, Pircher H (2007) Abrogation of CCL21 chemokine function by transgenic over-expression impairs T cell immunity to local infections. Int Immunol 19(11):1281–1289PubMedCrossRefGoogle Scholar
  60. 60.
    Brewig N, Kissenpfennig A, Malissen B, Veit A, Bickert T, Fleischer B, Mostbock S, Ritter U (2009) Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. J Immunol 182(2):774–783PubMedCrossRefGoogle Scholar
  61. 61.
    Fromm PD, Kling J, Mack M, Sedgwick JD, Korner H (2012) Loss of TNF signaling facilitates the development of a novel Ly-6C(low) macrophage population permissive for Leishmania major infection. J Immunol 188(12):6258–6266PubMedCrossRefGoogle Scholar
  62. 62.
    Gonzalez-Leal IJ, Roger B, Schwarz A, Schirmeister T, Reinheckel T, Lutz MB, Moll H (2014) Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection. PLoS Negl Trop Dis 8(9):e3194. Scholar
  63. 63.
    Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm GW, Kopf M (2015) T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med 212(4):555–568PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Schatz V, Strussmann Y, Mahnke A, Schley G, Waldner M, Ritter U, Wild J, Willam C, Dehne N, Brune B, McNiff JM, Colegio OR, Bogdan C, Jantsch J (2016) Myeloid cell-derived HIF-1alpha promotes control of Leishmania major. J Immunol 197(10):4034–4041PubMedCrossRefGoogle Scholar
  65. 65.
    Paul C, Wolff S, Zapf T, Raifer H, Feyerabend TB, Bollig N, Camara B, Trier C, Schleicher U, Rodewald HR, Lohoff M (2016) Mast cells have no impact on cutaneous leishmaniasis severity and related Th2 differentiation in resistant and susceptible mice. Eur J Immunol 46(1):114–121PubMedCrossRefGoogle Scholar
  66. 66.
    Amer EI, Eissa MM, Mossallam SF (2016) Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis. J Parasit Dis 40(2):475–484PubMedCrossRefGoogle Scholar
  67. 67.
    Ivens AC, Lewis SM, Bagherzadeh A, Zhang L, Chan HM, Smith DF (1998) A physical map of the Leishmania major Friedlin genome. Genome Res 8(2):135–145PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nicolle C (1908) Nouvelles acquisitions sur le kala-azar: culture; inoculation au chien; etiologie. Compte rendu hebdomadaire des Sciences de I’dcademie des Sciences, Paris 146:498–499Google Scholar
  69. 69.
    Nicolle C (1908) Culture du parasite du bouton d’orient. Compte rendu hebdomadaire des Sciences de l’Academie des Sciences, Paris 146:842–843Google Scholar
  70. 70.
    Hockmeyer WT, Kager PA, Rees PH, Hendricks LD (1981) The culture of Leishmania donovani in schneider’s insect medium: its value in the diagnosis and management of patients with visceral leishmaniasis. Trans R Soc Trop Med Hyg 75(6):861–863PubMedCrossRefGoogle Scholar
  71. 71.
    Howard MK, Pharoah MM, Ashall F, Miles MA (1991) Human urine stimulates growth of Leishmania in vitro. Trans R Soc Trop Med Hyg 85:477–479PubMedCrossRefGoogle Scholar
  72. 72.
    Lima HC, Bleyenberg JA, Titus RG (1997) A simple method for quantifying Leishmania in tissues of infected animals. Parasitol Today 13:80–82PubMedCrossRefGoogle Scholar
  73. 73.
    Prajeeth CK, Haeberlein S, Sebald H, Schleicher U, Bogdan C (2011) Leishmania-infected macrophages are targets of NK cell-derived cytokines, but not of NK cell cytotoxicity. Infect Immun 79:2699–2708PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Blos M, Schleicher U, Rocha FJ, Meissner U, Röllinghoff M, Bogdan C (2003) Organ-specific and stage-dependent control of Leishmania major infection by inducible nitric oxide synthase and phagocyte NADPH oxidase. Eur J Immunol 33:1224–1234PubMedCrossRefGoogle Scholar
  75. 75.
    Schleicher U, Liese J, Justies N, Mischke T, Haeberlein S, Sebald H, Kalinke U, Weiss S, Bogdan C (2018) Type I interferon signaling is required for CpG-oligodesoxynucleotide-induced control of Leishmania major, but not for spontaneous cure of subcutaneous primary or secondary L. major infection. Front Immunol 9:79. Scholar
  76. 76.
    Taswell C (1981) Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol 126(4):1614–1619PubMedGoogle Scholar
  77. 77.
    Titus RG, Marchand M, Boon T, Louis JA (1985) A limiting dilution assay for quantifying Leishmania major in tissues of infected mice. Parasite Immunol 7:545–555PubMedCrossRefGoogle Scholar
  78. 78.
    Cossarizza A, Chang HD, Radbruch A, Akdis M, Andra I, Annunziato F, Bacher P, Barnaba V, Battistini L, Bauer WM, Baumgart S, Becher B, Beisker W, Berek C, Blanco A, Borsellino G, Boulais PE, Brinkman RR, Buscher M, Busch DH, Bushnell TP, Cao X, Cavani A, Chattopadhyay PK, Cheng Q, Chow S, Clerici M, Cooke A, Cosma A, Cosmi L, Cumano A, Dang VD, Davies D, De Biasi S, Del Zotto G, Della Bella S, Dellabona P, Deniz G, Dessing M, Diefenbach A, Di Santo J, Dieli F, Dolf A, Donnenberg VS, Dorner T, Ehrhardt GRA, Endl E, Engel P, Engelhardt B, Esser C, Everts B, Dreher A, Falk CS, Fehniger TA, Filby A, Fillatreau S, Follo M, Forster I, Foster J, Foulds GA, Frenette PS, Galbraith D, Garbi N, Garcia-Godoy MD, Geginat J, Ghoreschi K, Gibellini L, Goettlinger C, Goodyear CS, Gori A, Grogan J, Gross M, Grutzkau A, Grummitt D, Hahn J, Hammer Q, Hauser AE, Haviland DL, Hedley D, Herrera G, Herrmann M, Hiepe F, Holland T, Hombrink P, Houston JP, Hoyer BF, Huang B, Hunter CA, Iannone A, Jack HM, Javega B, Jonjic S, Juelke K, Jung S, Kaiser T, Kalina T, Keller B, Khan S, Kienhofer D, Kroneis T, Kunkel D, Kurts C, Kvistborg P, Lannigan J, Lantz O, Larbi A, LeibundGut-Landmann S, Leipold MD, Levings MK, Litwin V, Liu Y, Lohoff M, Lombardi G, Lopez L, Lovett-Racke A, Lubberts E, Ludewig B, Lugli E, Maecker HT, Martrus G, Matarese G, Maueroder C, McGrath M, McInnes I, Mei HE, Melchers F, Melzer S, Mielenz D, Mills K, Mirrer D, Mjosberg J, Moore J, Moran B, Moretta A, Moretta L, Mosmann TR, Muller S, Muller W, Munz C, Multhoff G, Munoz LE, Murphy KM, Nakayama T, Nasi M, Neudorfl C, Nolan J, Nourshargh S, O'Connor JE, Ouyang W, Oxenius A, Palankar R, Panse I, Peterson P, Peth C, Petriz J, Philips D, Pickl W, Piconese S, Pinti M, Pockley AG, Podolska MJ, Pucillo C, Quataert SA, Radstake T, Rajwa B, Rebhahn JA, Recktenwald D, Remmerswaal EBM, Rezvani K, Rico LG, Robinson JP, Romagnani C, Rubartelli A, Ruckert B, Ruland J, Sakaguchi S, Sala-de-Oyanguren F, Samstag Y, Sanderson S, Sawitzki B, Scheffold A, Schiemann M, Schildberg F, Schimisky E, Schmid SA, Schmitt S, Schober K, Schuler T, Schulz AR, Schumacher T, Scotta C, Shankey TV, Shemer A, Simon AK, Spidlen J, Stall AM, Stark R, Stehle C, Stein M, Steinmetz T, Stockinger H, Takahama Y, Tarnok A, Tian Z, Toldi G, Tornack J, Traggiai E, Trotter J, Ulrich H, van der Braber M, van Lier RAW, Veldhoen M, Vento-Asturias S, Vieira P, Voehringer D, Volk HD, von Volkmann K, Waisman A, Walker R, Ward MD, Warnatz K, Warth S, Watson JV, Watzl C, Wegener L, Wiedemann A, Wienands J, Willimsky G, Wing J, Wurst P, Yu L, Yue A, Zhang Q, Zhao Y, Ziegler S, Zimmermann J (2017) Guidelines for the use of flow cytometry and cell sorting in immunological studies. Eur J Immunol 47(10):1584–1797PubMedCrossRefGoogle Scholar
  79. 79.
    Dwyer DM, Langreth SG, Dwyer NK (1974) Evidence for a polysaccharide surface coat in the developmental stages of Leishmania donovani: a fine structure-cytochemical study. Z Parasitenkd 43(4):227–249PubMedCrossRefGoogle Scholar
  80. 80.
    Ambit A, Woods KL, Cull B, Coombs GH, Mottram JC (2011) Morphological events during the cell cycle of Leishmania major. Eukaryot Cell 10(11):1429–1438. Scholar
  81. 81.
    Wheeler RJ, Gluenz E, Gull K (2011) The cell cycle of Leishmania: morphogenetic events and their implications for parasite biology. Mol Microbiol 79(3):647–662PubMedCrossRefGoogle Scholar
  82. 82.
    Hand WL (1984) Inhibition of cell-free oxidative bactericidal activity by erythrocytes and hemoglobin. Infect Immun 44:465–468PubMedPubMedCentralGoogle Scholar
  83. 83.
    Martins R, Maier J, Gorki AD, Huber KV, Sharif O, Starkl P, Saluzzo S, Quattrone F, Gawish R, Lakovits K, Aichinger MC, Radic-Sarikas B, Lardeau CH, Hladik A, Korosec A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth SC, Decker T, Bennett KL, Kubicek S, Sixt M, Superti-Furga G, Knapp S (2016) Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nat Immunol 17(12):1361–1372PubMedCrossRefGoogle Scholar
  84. 84.
    Fischer MR, John D, Kautz-Neu K, Schermann AI, Schwonberg K, von Stebut E (2013) Animal model for cutaneous leishmaniasis. Methods Mol Biol 961:389–402PubMedCrossRefGoogle Scholar
  85. 85.
    Hulspas R, O'Gorman MR, Wood BL, Gratama JW, Sutherland DR (2009) Considerations for the control of background fluorescence in clinical flow cytometry. Cytometry B Clin Cytom 76(6):355–364PubMedCrossRefGoogle Scholar
  86. 86.
    Solbach W, Lohoff M, Streck H, Rohwer P, Röllinghoff M (1987) Kinetics of cell-mediated immunity developing during the course of Leishmania major infection in ‘healer’ and ‘non-healer’ mice: progressive impairment of response to and generation of interleukin-2. Immunol 62:485–492Google Scholar
  87. 87.
    Stenger S, Donhauser N, Thüring H, Röllinghoff M, Bogdan C (1996) Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase. J Exp Med 183:1501–1514PubMedCrossRefGoogle Scholar
  88. 88.
    Kebaier C, Louzir H, Chenik M, Salah AB, Dellagi K (2001) Heterogeneity of wild Leishmania major isolates in experimental murine pathogenicity and specific immune response. Infect Immun 69:4906–4915PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Kopf M, Brombacher F, Köhler G, Kienzle G, Widmann K-H, Lefrang K, Humborg C, Ledermann B, Solbach W (1996) IL-4 deficient BALB/c mice resist infection with Leishmania major. J Exp Med 184:1127–1136PubMedCrossRefGoogle Scholar
  90. 90.
    Noben-Trauth N, Kropf P, Müller I (1996) Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science 271:987–990PubMedCrossRefGoogle Scholar
  91. 91.
    Lira R, Mendez S, Carrera L, Jaffe C, Neva F, Sacks D (1998) Leishmania tropica: the identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease. Exp Parasitol 89(3):331–342PubMedCrossRefGoogle Scholar
  92. 92.
    Anderson CF, Lira R, Kamhawi S, Belkaid Y, Wynn TA, Sacks D (2008) IL-10 and TGF-beta control the establishment of persistent and transmissible infections produced by Leishmania tropica in C57BL/6 mice. J Immunol 180(6):4090–4097PubMedCrossRefGoogle Scholar
  93. 93.
    Youssef MY, Eissa MM, el-Naga IF, el-Gowhary SH (1996) Dissemination of leishmania to organs of mice experimentally infected with Leishmania tropica. J Egypt Soc Parasit 26(3):719–731Google Scholar
  94. 94.
    Pérez H, Labrador F, Torrealba J (1979) Variations in the response of five strains of mice to Leishmania mexicana. Int J Parasitol 9:27–32PubMedCrossRefGoogle Scholar
  95. 95.
    Aguilar Torrentera F, Lambot MA, Laman JD, Van Meurs M, Kiss R, Noel JC, Carlier Y (2002) Parasitic load and histopathology of cutaneous lesions, lymph node, spleen, and liver from BALB/c and C57BL/6 mice infected with Leishmania mexicana. Am J Trop Med Hyg 66(3):273–279PubMedCrossRefGoogle Scholar
  96. 96.
    Buxbaum LU, Uzonna JE, Goldschmidt MH, Scott P (2002) Control of New World cutaneous leishmaniasis is IL-12-independent, but STAT4 dependent. Eur J Immunol 32:3206–3215PubMedCrossRefGoogle Scholar
  97. 97.
    Rogers ME, Ilg T, Nikolaev AV, Ferguson MA, Bates PA (2004) Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature 430(6998):463–467PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Afonso LC, Scott P (1993) Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. Infect Immun 61(7):2952–2959PubMedPubMedCentralGoogle Scholar
  99. 99.
    Cortes DF, Carneiro MB, Santos LM, Souza TC, Maioli TU, Duz AL, Ramos-Jorge ML, Afonso LC, Carneiro C, Vieira LQ (2010) Low and high-dose intradermal infection with Leishmania major and Leishmania amazonensis in C57BL/6 mice. Mem Inst Oswaldo Cruz 105(6):736–745PubMedCrossRefGoogle Scholar
  100. 100.
    DeKrey GK, Lima HC, Titus RG (1998) Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun 66:827–829PubMedPubMedCentralGoogle Scholar
  101. 101.
    Lima GH, DeKrey GK, Titus RG (1999) Resolution of an infection with Leishmania braziliensis confers complete protection to a subsequent challenge with Leishmania major in BALB/c mice. Mem Inst Oswaldo Cruz 94:71–76PubMedCrossRefGoogle Scholar
  102. 102.
    Maioli TU, Takane E, Arantes RME, Fietto JLR, Afonso LCC (2004) Immune response induced by New World Leishmania species in C57BL/6 mice. Parasitol Res 94:207–212PubMedCrossRefGoogle Scholar
  103. 103.
    Soares Rocha FJ, Schleicher U, Mattner J, Alber G, Bogdan C (2007) Cytokines, signaling pathways, and effector molecules required for the control of Leishmania (Viannia) braziliensis in mice. Infect Immun 75:3823–3832CrossRefGoogle Scholar
  104. 104.
    de Moura TR, Novais FO, Oliveira F, Clarencio J, Noronha A, Barral A, Brodskyn C, de Oliveira CI (2005) Toward a novel experimental model of infection to study American cutaneous leishmaniasis caused by Leishmania braziliensis. Infect Immun 73:5827–5834PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Ives A, Ronet C, Prevel F, Ruzzante G, Fuertes-Marraco S, Schutz F, Zangger H, Revaz-Breton M, Lye LF, Hickerson SM, Beverley SM, Acha-Orbea H, Launois P, Fasel N, Masina S (2011) Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science 331(6018):775–778PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Hartley MA, Bourreau E, Rossi M, Castiglioni P, Eren RO, Prevel F, Couppie P, Hickerson SM, Launois P, Beverley SM, Ronet C, Fasel N (2016) Leishmaniavirus-dependent metastatic leishmaniasis is prevented by blocking IL-17A. PLoS Pathog 12(9):e1005852. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Christian Bogdan
    • 1
    • 2
    Email author
  • Andrea Debus
    • 1
  • Heidi Sebald
    • 1
  • Baplu Rai
    • 1
  • Johanna Schäfer
    • 1
  • Stephanie Obermeyer
    • 1
  • Ulrike Schleicher
    • 1
    • 2
  1. 1.Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und HygieneFriedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum ErlangenErlangenGermany
  2. 2.Medical Immunology Campus ErlangenFAU Erlangen-NürnbergErlangenGermany

Personalised recommendations