Invasion, control and persistence of Leishmania parasites

Current Opinion in Immunology

Volumn 8, Issue 4, 1996, Pages 517-525

  Bogdan, Christian ^a   Gessner, André ^a   Werner, Solbach ^a   Martin, Röllinghoff ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 12;

HOST RESISTANCE; IMMUNOPATHOGENESIS; IMMUNOREGULATION; LEISHMANIASIS; MACROPHAGE; PARASITE IMMUNITY; REVIEW; T LYMPHOCYTE;

EID: 0029761631     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(96)80040-9     Document Type: Article

References (64)

1. Titus RG, Theodos CM, Shankar A, Hall LR. Interactions between Leishmania major and macrophages. Zwilling T, Eisenstein T. Macrophage - Pathogen Interactions. 1993;437-459 Marcel Dekker, New York.
2. Reiner SL, Locksley RM. The regulation of immunity to Leishmania major. Annu Rev Immunol. 13:1995;151-177.
3. Bogdan C, Röllinghoff M. The impact of the type 1 and type 2 T helper cell concept on novel vaccine design with emphasis on protection against Leishmania parasites. Kaufmann SHE. Concepts in Vaccine Development. 1996;143-180 Walter de Gruyter, Berlin.
4. Aebischer T. Recurrent cutaneous leishmaniasis: a role for persistent parasites. Parasitol Today. 10:1994;25-28.
5. Sacks DL, Pimenta PFP, McConville MJ, Schneider P, Turco SJ. Stage-specific binding of Leishmania donovani to the sand fly vector midgut is regulated by conformational changes in the abundant surface lipophosphoglycan. of outstanding interest J Exp Med. 181:1995;685-697 This paper offers a remarkable explanation for the stage specificity of promastigote attachment in the vector midgut and also for the enhanced infectivity of metacyclic Leishmania.
6. Kelleher M, Moody SF, Mirabile P, Osborn AH, Bacic A, Handman E. Lipophosphoglycan blocks attachment of Leishmania major amastigotes to macrophage. of special interest Infect Immun. 63:1995;43-50 Unlike L. donovani or L. mexicana amastigotes, L. major amastigotes exhibit LPG (on their surface and in their flagellar pocket) which apparently mediates attachment to peritoneal macrophages in a complement-independent fashion.
7. Blank C, Bogdan C, Bauer C, Erb K, Moll H. Murine epidermal Langerhans cells do not express inducible nitric oxide synthase. Eur J Immunol. 26:1996;792-796.
8. Proudfoot L, O'Donnell CA, Liew FY. Glycoinositolphospholipids of Leishmania major inhibit nitric oxide synthesis and reduce leishmanicidal activity in murine macrophages. of special interest Eur J Immunol. 25:1995;745-750 This is the first study showing that a Leishmania product is able to modulate iNOS.
9. Jardim A, Funk V, Caprioli RM, Olafson RW. Isolation and characterization of the Leishmania donovani kinetoplastid membrane protein-11, a major immunoreactive membrane glycoprotein. Biochem J. 305:1995;307-313.
10. Hall LR, Titus RG. Sandfly vector saliva selectively modulates macrophage functions that inhibit killing of Leishmania major and nitric oxide production. of special interest J Immunol. 155:1995;3501-3506 This study illustrates that laboratory infections lack an important cofactor which presumably supports the initial survival of Leishmania after natural transmission.
11. Barral-Netto M, Barral A, Brownell CE, Skeiky YAW, Ellingsworth LR, Twardzik DR, Reed SG. Transforming growth factor-β in leishmanial infection: a parasite escape mechanism. Science. 257:1992;545-548.
12. Stenger S, Thüring H, Röllinghoff M, Bogdan C. Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major. J Exp Med. 180:1994;783-793.
13. Carrera L, Gazzinelli RT, Badolato R, Hieny S, Müller W, Kühn R, Sacks DL. Leishmania promastigotes selectively inhibit interleukin-12 induction in bone marrow-derived macrophages from susceptible and resistant mice. of special interest J Exp Med. 183:1996;515-526 Leishmania promastigotes not only fail to induce IL-12, but also suppress IL-12 induction by secondary stimuli (LPG, M. tuberculosis). The suppression is independent of lipopolysaccharide, and concurrently induced IL-10, and is observed with both cutaneous and visceral strains of Leishmania.
14. Bogdan C, Nathan C. Modulation of macrophage function by transforming growth factor-β, interleukin 4 and interleukin 10. Ann NY Acad Sci. 685:1993;713-739.
15. Buelens C, Willems F, Delvaux A, Piérard G, Delville J-P, Velu T, Goldman M. Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells. Eur J Immunol. 25:1995;2668-2672.
16. Kaye PM. Costimulation and the regulation of antimicrobial immunity. Immunol Today. 16:1995;423-427.
17. Nandan D, Reiner NE. Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signalling through Janus kinases and Stat1. of special interest Infect Immun. 63:1996;4495-4500 This is the first study demonstrating that an intracellular parasite affects the IFN-γ signalling pathway.
18. De Souza-Leao S, Lang T, Prina E, Hellio R, Antoine JC. Intracellular Leishmania amazonensis amastigotes internalize and degrade MHC class II molecules of their host cells. J Cell Sci. 108:1995;3219-3231.
19. Biron CA, Gazzinelli RT. Effects of IL-12 in immune responses to microbial infections: a key mediator in regulating disease outcome. Curr Opin Immunol. 7:1995;485-496.
20. + T cells during initiation of infection. J Exp Med. 179:1994;447-456.
21. Scharton-Kersten T, Afonso LCC, Wysocka M, Trinchieri G, Scott P. IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis. of outstanding interest J Immunol. 154:1995;5320-5330 Currently the only study which provides evidence for the in vivo production of IL-12 protein within the first twenty four hours of infection. Enhanced production of TGF-β (as reported previously in [13]) appears to antagonize the function of IL-12 in BALB/c mice.
22. Skeiky YAW, Guderian JA, Benson DR, Bacelar O, Carvalho EM, Kubin M, Badaro R, Trinchieri G, Reed SG. A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin-12. of outstanding interest J Exp Med. 181:1995;1527-1537 This is the first recombinant parasite protein (LelF) shown to trigger IL-12 production. However, anti-IFN-γ treatment reduced the IL-12 (p40) release by approximately 60%, indicating that a significant portion of the IL-12 produced is secondary to the induction of IFN-γ. The protein is an attractive candidate for vaccination purposes.
23. Mougneau E, Altare F, Wakil AE, Zheng S, Coppola T, Wang Z-E, Waldmann R, Locksley RM, Glaichenhaus N. Expression cloning of a protective Leishmania antigen. of outstanding interest Science. 268:1995;563-566 In an elegant approach, L. major proteins from a cDNA library were expressed as fusions with an influenza haemagglutinin (HA) anchor. Binding by an anti-HA-antibody allowed for Fc-receptor-mediated uptake of pools of proteins by macrophages, which were then tested for their ability to stimulate a T-cell hybridoma derived from an L. major-specific protective T cell line.
24. Campos-Neto A, Soong L, Cordova JL, Sant-Angelo D, Skeiky YAW, Ruddie NH, Reed SG, Janeway C, McMahon-Pratt D. Cloning and expression of a Leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class II molecules of infected macrophages. of special interest J Exp Med. 182:1995;1423-1433 A Leishmania peptide was isolated from the MHC class II molecules of L. donovani infected macrophages and used for the cloning of the respective Leishmania donor protein. This protein stimulated T cells from L. major-, L. mexicana- or L. donovani-infected mice to produce high levels of IFN-γ, but not of IL-4.
25. Sypek JP, Chung CL, Mayor SHE, Subramanyam JM, Goldman SJ, Sieburth DS, Wolf SF, Schaub RG. Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response. J Exp Med. 177:1993;1797-1802.
26. Heinzel FP, Rerko RM, Ahmed F, Pearlman E. Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice. J Immunol. 155:1995;730-739.
27. Heinzel FP, Schoenhaut DS, Rerko RM, Rosser LE, Gately MK. Recombinant interleukin 12 cures mice infected with Leishmania major. J Exp Med. 177:1993;1505-1509.
28. Wang Z-E, Zheng S, Corry DB, Dalton DK, Seder RA, Reiner SL, Locksley RM. Interferon-γ-independent effects of interleukin-12 administered during acute or established infection due to Leishmania major. Proc Natl Acad Sci USA. 91:1994;12932-12936.
29. Ritter U, Moll H, Laskay T, Bröcker E-B, Velazco O, Becker I, Gillitzer R. Differential expression of chemokines in skin lesions of patients with localized and diffuse American cutaneous leishmaniasis. of special interest J Infect Dis. 173:1996;699-709 In the lesions of patients with localized cutaneous leishmaniasis, high levels of macrophage chemoattractant protein (MCP)-1 and moderate levels of macrophage inhibitory protein (MIP)-1α were detected, whereas in lesions from patients with diffuse, non-curing cutaneous leishmaniasis, MIP-1α expression was much more prominent than that of MCP-1. The relevance of these findings to pathogenesis remains to be elucidated.
30. Afonso LCC, Scharton TM, Vieira LQ, Wysocka M, Trinchieri G, Scott P. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science. 263:1994;235-237.
31. Nabors GS, Afonso LCC, Farrell JP, Scott P. Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and pentostam. of special interest Proc Natl Acad Sci USA. 92:1995;3142-3146 See annotation [32].
32. Murray HW, Hariprashad J. Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis. of special interest J Exp Med. 181:1995;387-391 Along with [31], this study suggests the use of IL-12 for the treatment of established Leishmania infections.
33. Mocci S, Coffman RL. Induction of a Th2 population from a polarized Leishmania-specific Th1 population by in vitro culture with IL-4. J Immunol. 154:1995;3779-3787.
34. Wynn TA, Jankovic D, Hieny S, Zioncheck K, Jardieu P, Cheever AW, Sher A. IL-12 exacerbates rather than suppresses T helper 2-dependent pathology in the absence of endogenous IFN-γ J Immunol. 154:1995;3999-4009.
35. + effector cells default to the Th2 pathway in interferon-γ-deficient mice infected with Leishmania major. J Exp Med. 179:1994;1367-1371.
36. + T cell response. of special interest J Exp Med. 181:1995;961-971 The data show that a lack of functional IFN-γ does not lead to a Th2 response in mice coming from resistant backgrounds.
37. Vieira LQ, Goldschmidt M, Nashleanas M, Pfeffer K, Mak T, Scott P. Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection with Leishmania major, but control parasite replication. in press J Immunol. 1996.
38. Locksley RM, Reiner SL, Hatam F, Littman DR, Killeen N. Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science. 261:1993;1448-1451.
39. Chakkalath HR, Theodos CM, Markowitz JS, Grusby MJ, Glimcher LH, Titus RG. Class II major histocompatibility complex-deficient mice initially control an infection with Leishmania major but succumb to the disease. J Infect Dis. 171:1995;1302-1308.
40. Kennedy MK, Picha KS, Fanslow WS, Grabstein KH, Alderson MR, Clifford KN, Chin WA, Mohler KM. CD40/CD40 ligand interactions are required for T cell-dependent production of interleukin-12 by mouse macrophages. Eur J Immunol. 26:1996;370-378.
41. Stout RD, Suttles J, Xu J, Grewal I, Flavell RA. Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice. of special interest J Immunol. 156:1996;8-11 This study suggests the existence of two sequential phases of interaction in the activation of macrophages by contact with T cells. The first phase (<24 h of stimulation) is dependent on the CD40 - CD40L receptor system.
42. Kamanaka M, Yu P, Yasui T, Yoshida K, Kawabe T, Horii T, Kishimoto T, Kikutani H. Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity. of outstanding interest Immunity. 4:1996;275-281 See annotation [44].
43. Soong L, Xu J-C, Grewal IS, Kima P, Sun J, Longley BJ, Ruddle NH, McMahon-Pratt D, Flavell RA. Disruption of CD40 - CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection. of outstanding interest Immunity. 4:1996;263-273 See annotation [44].
44. Campbell KA, Ovendale PJ, Kennedy MK, Fanslow WC, Reed SG, Maliszewski CR. CD40 ligand is required for protective cell-mediated immunity to Leishmania major. of outstanding interest Immunity. 4:1996;283-289 The first study to demonstrate the importance of the CD40 - CD40L interaction for the generation of a protective anti-Leishmania immune response.
45. Corry DB, Reiner SL, Linsley PS, Locksley RM. Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis. J Immunol. 153:1994;4142-4148.
46. -/- macrophages questions some of the conclusions drawn by the authors.
47. G-monomethyl-arginine in vitro and in vivo. Eur J Pharmacol. 294:1995;703-712.
48. Thüring H, Stenger S, Gmehling D, Röllinghoff M, Bogdan C. Lack of inducible nitric oxide synthase activity in T cell-clones and lymphocytes from naive and Leishmania major-infected mice. of special interest Eur J Immunol. 25:1995;3229-3234 The first study which analyzed primary T lymphocytes on a single-cell level for the expression of iNOS.
49. Vouldoukis I, Riveros-Moreno V, Dugas B, Quaaz F, Bécherel P, Debré P, Moncada S, Mossalayi MD. The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the FcεRII/CD23 surface antigen. of outstanding interest Proc Natl Acad Sci USA. 92:1995;7804-7808 The first study which convincingly demonstrated the expression and antimicrobial function of iNOS potein and activity in human macrophages. iNOS induction is dependent on the surface expression of CD23, which is upregulated by previous treatment with IL-4 or the infection with L. major.
50. Noben-Trauth N, Kropf P, Müller I. Susceptibility to Leishmania major infection in interleukin-4-deficient mice. of special interest Science. 271:1996;987-990 This provocative paper questions one of the core hypotheses on the immunopathogenesis of non-curing L. major infection.
51. -/- mice infected with L. mexicana. In contrast, deletion of the IL-4 gene does not improve the course of infection in L. donovani-infected mice.
52. Hoerauf A, Solbach W, Röllinghoff M, Gessner A. Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease. Int Immunol. 7:1995;1879-1884.
53. Satoskar A, Alexander J. Sex-determined susceptibility and differential IFN-γ and TNF-α mRNA expression in DBA/2 mice infected with Leishmania mexicana. Immunology. 84:1995;1-4.
54. Nabors GS, Nolan T, Croop W, Li J, Farrell JP. 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. of special interest Parasite Immunol. 17:1995;569-579 This paper emphasizes the impact of a widely neglected parameter on the course of Leishmania infections. (BALB/c x C57BL/6)F1 mice developed progressive disease when inoculated with L. major in the dorsal skin, but healed infections in the footpad. Healer and non-healer mice ultimately displayed a Th1 or Th2 response, respectively, but there was no difference in the IFN-γ and IL-4 expression during the first two weeks of infection.
55. Krishnan L, Guilbert LI, Russell AS, Wegmann TG, Mosmann TR, Belosevic M. Pregnancy impairs resistance of CS7BL/6 mice to Leishmania major infection and causes decreased antigen-specific IFN-γ responses and increased production of T helper 2 cytokines. J Immunol. 156:1996;644-652.
56. Cabrera M, Shaw M-A, Sharples C, Williams H, Castes M, Convit J, Blackwell JM. Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis. of special interest J Exp Med. 182:1995;1259-1264 The first study which succeeds in detecting putative genetic predispositions to severe cutaneous leishmaniasis in humans. The risk of developing mucocutaneous leishmaniasis following infection with L. braziliensis is increased in patients with certain allelic polymorphisms in the promotor region of the TNF-α and TNF-β genes affecting the production of these cytokines.
57. Güler ML, Gorham JD, Hsieh C-S, Mackey AJ, Steen RG, Dietrich WF, Murphy KM. Genetic susceptibility to Leishmania: IL-12 responsiveness in Th1 cell development. of outstanding interest Science. 271:1996;984-987 The authors extended their previously described in vitro system [61] by analyzing the influence of the cytokine milieu on the long term responsiveness to IL-12 of T cells from transgenic mice of different genetic backgrounds. An elegant piece of work, which should have had a more accurate and less misleading title, since it does not deal with Leishmania infections.
58. Shankar AH, Titus RG. T cell and non-T cell compartments can independing determine resistance to Leishmania major. of outstanding interest J Exp Med. 181:1995;845-855 With the help of a classical immunological technique (bone marrow chimeras) the authors challenge those who believe that resistance and susceptibility are merely dependent on the T-cell compartment.
59. Laskay T, Diefenbach A, Röllinghoff M, Solbach W. Early parasite containment is decisive for resistance to Leishmania major infection. of special interest Eur J Immunol. 25:1995;2220-2227 This work describes a strikingly different pattern of parasite spreading as the first (within 10 h) detectable difference between BALB/c mice and resistant mouse strains after infection with L. major.
60. + T cells as the early source of IL-4 in L. major infections.
61. Hsieh C-S, Macatonia SE, O'Garra A, Murphy KM. T cell genetic background determines default T helper phenotype development in vitro. of outstanding interest J Exp Med. 181:1995;713-721 See annotation [57].
62. + T cells are important for the balance between protective and pathogenic cell-mediated immunity. of special interest J Exp Med. 179:1994;589-600.
63. Stenger S, Donhauser N, Thüring H, Röllinghoff M, Bogdan C. Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase. of special interest J Exp Med. 183:1996;1501-1515 For the first time, iNOS is shown to be crucial for the control of a latent infection in vivo. This study also defines the localization of iNOS and persistent parasites in situ.
64. Moll H, Flohé S, Röllinghoff M. Dendritic cells in Leishmania major-immune mice harbor persistent parasites and mediate an antigen-specific T cell immune response. Eur J Immunol. 25:1995;693-699.