1921
Volume 71, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

While the response to is well characterized in mice, there is much less known about the human immune response, particularly early after exposure to the parasite. Therefore, we developed a primary (PIV) system that allowed us to address these questions. We co-cultured peripheral blood mononuclear cells from -naive donors with parasites and found that the responding PIV cells produced interferon-γ and interleukin-12 (IL-12). When restimulated, these PIV cells also occasionally produced IL-5. Both CD4 and CD8 cells and both HLA class I and II cell activation pathways appeared to play a role in the PIV system, and cell activation was dependent upon the presence of antigen-presenting cells. Moreover, PIV cells generated with showed considerable cross-reactivity with other species of . Finally, the PIV cells augmented intracellular killing of when they were co-cultured with macrophages infected with the parasite.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2004.71.568
2004-11-01
2018-12-17
Loading full text...

Full text loading...

/deliver/fulltext/14761645/71/5/0700568.html?itemId=/content/journals/10.4269/ajtmh.2004.71.568&mimeType=html&fmt=ahah

References

  1. World Health Organization, 2001. WHO information by topics or disease: http://www.who.int/emc/diseases/leish/index.html.
  2. Launois P, Tacchini-Cottier F, Parra-Lopez C, Louis JA, 1998. Cytokines in parasitic diseases: the example of cutaneous leishmaniasis. Int Rev Immunol 17 : 157–180. [Google Scholar]
  3. Solbach W, Laskay T, 2000. The host response to Leishmania infection. Adv Immunol 74 : 275–317. [Google Scholar]
  4. Etges R, Muller I, 1998. Progressive disease or protective immunity to Leishmania major infection: the result of a network of stimulatory and inhibitory interactions. J Mol Med 76 : 372–390. [Google Scholar]
  5. Louis JA, Conceicao-Silva F, Himmelrich H, Tacchini-Cottier F, Launois P, 1998. Anti-leishmania effector functions of CD4+ Th1 cells and early events instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice. Adv Exp Med Biol 452 : 53–60. [Google Scholar]
  6. Rogers KA, DeKrey GK, Mbow ML, Gillespie RD, Brodskyn CI, Titus RG, 2002. Type 1 and type 2 responses to Leishmania major. FEMS Microbiol Lett 209 : 1–7. [Google Scholar]
  7. Shankar A, Titus RG, 1993. Leishmania major-specific, CD4+, MHC class-II-restricted T cells derived in vitro from lymphoid tissues of naive mice. J Exp Med 178 : 101–111. [Google Scholar]
  8. Soares MBP, David JR, Titus RG, 1997. An in vitro model for infection with Leishmania major that mimics the immune response in mice. Infect Immun 65 : 2837–2845. [Google Scholar]
  9. Kurtzhals JAL, Kemp M, Poulsens LK, Hansen MB, Kharazmi A, Theander TG, 1995. Interleukin-4 and interferon-gamma production by Leishmania stimulated peripheral blood mono-nuclear cells from nonexposed individuals. Scand J Immunol 41 : 343–349. [Google Scholar]
  10. Russo DM, Chakrabarti P, Higgins AY, 1999. Leishmania: naive human T cells sensitized with promastigote antigen and IL-12 develop into potent Th1 and CD8+ cytotoxic effectors. Exp Parasitol 93 : 161–170. [Google Scholar]
  11. Akuffo H, Maasho K, Howe R, 1993. Natural and acquired resistance to Leishmania: cellular activation by Leishmania aethiopica of mononuclear cells from unexposed individuals is through the stimulation of natural killer (NK) cells. Clin Exp Immunol 94 : 516–521. [Google Scholar]
  12. Nylen S, Mortber U, Kovalenko D, Satti I, Engstrom K, Bakhiet M, Akuffo H, 2001. Differential induction of cellular responses by live and dead Leishmania promastigotes in healthy donors. Clin Exp Immunol 124 : 43–53. [Google Scholar]
  13. Nylen S, Maasho K, Sonderstrom K, Ilg I, Akuffo H, 2003. Live Leishmania promastigotes can directly activate primary human natural killer cells to produce interferon-gamma. Clin Exp Immunol 131 : 457–467. [Google Scholar]
  14. Bourreau E, Collet M, Prevot G, Milon G, Ashimoff D, Hasagewa H, Parra-Lopez C, Launois P, 2002. IFN-gamma-producing CD45RA+CD8+ and IL-10-producing CD45RA-CD4+ T cells generated in response to LACK in naive subjects never exposed to Leishmania. Eur J Immunol 32 : 510–520. [Google Scholar]
  15. Titus RG, Kelso A, Louis JA, 1984. Intracellular destruction of Leishmania tropica by macrophages activated with macrophage activating factor/interferon. Clin Exp Immunol 55 : 157–165. [Google Scholar]
  16. Howard MK, Pharoah MM, Ashall F, Miles MA, 1991. Human urine stimulates growth of Leishmania in vitro. Trans R Soc Trop Med Hyg 85 : 477–479. [Google Scholar]
  17. Titus RG, Lima GC, Engers HD, Louis JA, 1984. Exacerbation of murine cutaneous leishmaniasis by adoptive transfer of parasite-specific helper T cell populations capable of mediating Leishmania major-specific delayed-type hypersensitivity. J Immunol 133 : 1594–1600. [Google Scholar]
  18. Goldrosen MH, Gannon PJ, Lutz M, Holyoke ED, 1977. Isolation of human peripheral blood lymphocytes: modification of double discontinuous density gradient of Ficoll-Hypaque. J Immunol Methods 14 : 15–17. [Google Scholar]
  19. Brodskyn CI, DeKrey GK, Titus RG, 2001. Influence of costimulatory molecules on immune response to Leishmania major by human cells in vitro. Infect Immun 69 : 665–672. [Google Scholar]
  20. Melby PC, Valencia-Pacheco G, Andrade-Narvaez F, 1996. Induction of macrophage killing of Leishmania donovani by human CD4+ T cell clones. Arch Med Res 4 : 473–479. [Google Scholar]
  21. Rogers KA, Titus RG, 2004. The human cytokine response to Leishmania major early after exposure to the parasite in vitro. J Parasitol 90 : 557–563. [Google Scholar]
  22. Murray HW, 1982. Cell mediated immune response in experimental visceral leishmaniasis II: oxygen dependent killing of intracellular Leishmania donovani amastigotes. J Immunol 129 : 351–357. [Google Scholar]
  23. Murray HW, Nathan CF, 1999. Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. J Exp Med 89 : 741–746. [Google Scholar]
  24. Chatelain R, Varkila K, Coffman RL, 1992. IL-4 induces a Th2 response in Leishmania major infected mice. J Immunol 148 : 1182–1187. [Google Scholar]
  25. Mocci S, Coffman RL, 1997. The mechanism of in vitro T helper cell type 1 to T helper cell type 2 switching in highly polarized Leishmania major specific T cell populations. J Immunol 158 : 1559–1564. [Google Scholar]
  26. Liew FY, Wei X-Q, Proudfoote L, 1997. Cytokines and nitric oxide as effector molecules against parasitic infections. Philos Trans R Soc Lond B Biol Sci 352 : 1311–1315. [Google Scholar]
  27. Herwaldt BL, 1999. Leishmaniasis. Lancet 354 : 1191–1199. [Google Scholar]
  28. Handman E, 2001. Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 14 : 229–243. [Google Scholar]
  29. Russo DM, Chakrabart P, Burns JM, 1998. Naïve human T cells develop into Th1 or Th0 effectors and exhibit cytotoxicity early after stimulation with Leishmania-infected macrophages. J Infect Dis 177 : 1345–1351. [Google Scholar]
  30. Kemp M, Hey AS, Kurtzhals JAL, Christensen CB, Gaafar A, Mustafa MD, Kordofani AA, Ismail A, Kharazmi A, Theander TG, 1994. Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis. Clin Exp Immunol 96 : 410–415. [Google Scholar]
  31. Akuffo H, Maasho K, Blostedt M, Hojeberg B, Britton S, Bakhiet M, 1997. Leishmania aethiopica derived from diffuse cutaneous leishmaniasis patients preferentially induce mRNA for IL-10 while those from localized leishmaniasis patients induce IFN-γ. J Infect Dis 175 : 737–741. [Google Scholar]
  32. Ajdary S, Alimohammadian MH, Eslami MB, Kemp K, Kharazmi A, 2000. Comparison of the immune profile of non-healing cutaneous leishmaniasis patients with those with active lesions and those who have recovered from infection. Infect Immun 68 : 1760–1764. [Google Scholar]
  33. Melby PC, Andrade-Narvaez FJ, Darnell BJ, Valencia-Pacheco G, Tryon VV, Palomo-Cetin A, 1994. Increased expression of proinflammatory cytokines in chronic lesions of human cutaneous leishmaniasis. Infect Immun 62 : 837–842. [Google Scholar]
  34. Gaafar A, Kharazmi A, Ismail A, Kemp M, Hey A, Christensen CB, Dafalla M, el Kadaro AY, el Hassan AM, Theander TG, 1995. Dichotomy of the T cell response to Leishmania antigens in patients suffering from cutaneous leishmaniasis; absence or scarcity of Th1 activity is associated with severe infections. Clin Exp Immunl 100 : 239–245. [Google Scholar]
  35. Melby PC, 1991. Experimental leishmaniasis in humans: review. Rev Infect Dis 13 : 1009–1017. [Google Scholar]
  36. Jaffe CL, 1999. Recent trends in vaccine development and immunization. Clin Dermatol 17 : 339–344. [Google Scholar]
  37. Lima HC, 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 : 71–76. [Google Scholar]
  38. Veras P, Brodskyn C, Balestieri F, Freitas L, Ramos A, Queiroz A, Barral A, Beverley S, Barral-Netto M, 1999. A dhfr-ts-Leishmania major knockout mutant cross-protects against Leishmania amazonensis. Mem Inst Oswaldo Cruz 94 : 491– 496. [Google Scholar]
  39. Bebars MA, el Serougi AO, Makled KM, Mikhael EM, Abou Gamra MM, el Sherbiny M, Mohareb AW, Mohammed EA, 2000. An experimental vaccine providing heterologous protection for Leishmania species in a murine model. J Egypt Soc Parasitol 30 : 137–156. [Google Scholar]
  40. 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 : 1373–1383. [Google Scholar]
  41. Lemos de Souza V, Ascencao Souza J, Correia Silva TM, Sampaio Tavares Veras P, Rodrigues De-Freitas LA, 2000. Different Leishmania species determine distinct profiles of immune and histopathological responses in CBA mice. Microbes Infect 2 : 1807–1815. [Google Scholar]
  42. Qi H, Ji J, Wanasen N, Soong L, 2004. Enhanced replication of Leishmania amazonensis amastigotes in gamma interferon-stimulated murine macrophages: implications for the pathogenesis of cutaneous leishmaniasis. Infect Immun 72 : 988–995. [Google Scholar]
  43. Lussow AR, Barrios C, van Embden J, van der Zee R, Verdini AS, Pessi A, Louis JA, Lambert P, Del Giudice G, 1991. Mycobacterial heat-shock proteins as carrier molecules. Eur J Immunol 21 : 2297–2302. [Google Scholar]
  44. Steimle V, Siegrist CA, Mottet A, Lisowska-Grospierre B, Mach B, 1994. Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science 265 : 106–109. [Google Scholar]
  45. Castes M, Cabrera M, Trujillo D, Convit J, 1988. T-cell subpopulations, expression of interleukin-2 receptor, and production of interleukin-2 and gamma interferon in human American cutaneous leishmaniasis. J Clin Microbiol 26 : 1207–1213. [Google Scholar]
  46. Isaza DM, Restrepo M, Restrepo R, Caceres-Dittmar G, Tapia FJ, 1996. Immunocytochemical and histopathologic characterization of lesions from patients with localized cutaneous leishmaniasis caused by Leishmania panamensis. Am J Trop Med Hyg 55 : 365–369. [Google Scholar]
  47. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL, 2002. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420 : 502–507. [Google Scholar]
  48. Wyler DJ, Beller DI, Sypek JP, 1987. Macrophage activation for antileishmanial defense by an apparently novel mechanism. J Immunol 138 : 1246–1249. [Google Scholar]
  49. Pompeu MML, Brodskyn C, Teixeira MJ, Clarencio J, Van Weyenberg J, Coelho ICB, Cardoso SA, Barral A, Barral-Netto M, 2001. Differences in gamma interferon production in vitro predict the pace of the in vivo response to Leishmania amazonensis in healthy volunteers. Infect Immun 69 : 7453–7460. [Google Scholar]
  50. Morris RV, Shoemaker CB, David JR, Lanzaro GC, Titus RG, 2001. Sand fly maxadilan exacerbates infection with Leishmania major and vaccinating against it protects against L. major infection. J Immunol 167 : 5226–5230. [Google Scholar]
  51. Valenzuela JG, Belkaid Y, Garfield MK, Mendez S, Kamhawi S, Rowton ED, Sacks DL, Ribeiro JMC, 2001. Toward a defined anti-Leishmania vaccine targeting vector antigens: Characterization of a protective salivary protein. J Exp Med 194 : 331–342. [Google Scholar]
  52. Rogers KA, Titus RG, 2003. Immunomodulatory effects of Maxadilan and Phlebotomus papatasi sand fly salivary gland lysates on human primary in vitro immune responses. Parasite Immunol 25 : 127–134. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2004.71.568
Loading
/content/journals/10.4269/ajtmh.2004.71.568
Loading

Data & Media loading...

  • Received : 22 Mar 2004
  • Accepted : 11 Jun 2004

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error