- INTRODUCTION
- MATERIALS AND METHODS
- Mice and parasites.
- Preparation of LmSEAgs and immunization of BALB/c mice.
- Infection of mice and determination of parasite numbers in cutaneous lesions or spleens.
- Cell proliferation and cytokine responses of cells from mice immunized with LmSEAgs.
- Cytokine responses post-infection with either L. braziliensis or L. donovani.
- Statistical analyses.
- RESULTS
- Lack of protection of BALB/c mice by vaccination with LmSEAgs against a subsequent challenge with L. braziliensis.
- Reduction of splenic parasite burden by vaccination with LmSEAgs after challenge with L. donovani.
- Proliferation and cytokines before infection.
- Production of elevated levels of type 2 cytokines in LmSEAgs-immunized mice after infection with L. braziliensis.
- Production of elevated levels of type 1 cytokines in LmSEAgs-immunized mice after infection with L. donovani.
- DISCUSSION
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1
World Health Organization, 2006. Leishmaniasis Control Home Page. Available from http://www.who.int/emc/diseases/leish/index.html
-
2
Desjeux P, UNAIDS, 1998. Leishmania and HIV in Gridlock. Geneva: World Health Organization. WHO/CTD/LEISH/98.1 and UNAIDS/98.23.
-
3
Pintado V, Martin-Rabadan P, Rivera ML, Moreno S, Bouza E, 2001. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 80 :54–73.
-
4
Mauel J, 2002. Vaccination against Leishmania infections. Curr Drug Targets Immune Endocr Metabol Disord 2 :201–226.
-
5
Handman E, 2001. Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 14 :229–243.
-
6
Veras P, Brodskyn C, Balestieri F, Freitas L, Ramos A, Queiroz A, Barral A, Beverley S, Barral-Netto M, 1999. A dhfr2ts2 Leishmania major knockout mutant cross-protects against Leishmania amazonensis. Mem Inst Oswaldo Cruz 94 :491–496.
-
7
Lainson R, Bray RS, 1966. Studies on the immunology and serology of leishmaniasis. II. Cross-immunity experiments among different forms of American cutaneous leishmaniasis in monkeys. Trans R Soc Trop Med Hyg 60 :526–532.
-
8
Tonui WK, Mejia JS, Hochberg L, Mbow ML, Ryan JR, Chan AST, Martin SK, Titus RG, 2004. Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L. major. Infect Immun 72 :5654–5661.
-
9
Ryan JR, Smithyman AM, Rajasekariah GH, Hochberg L, Stiteler JM, Martin SK, 2002. Enzyme-linked immunosorbent assay based on soluble promastigote antigen detects immuno-globulin M (IgM) and IgG antibodies in sera from cases of visceral leishmaniasis and cutaneous leishmaniasis. J Clin Microbiol 40 :1037–1043.
-
10
Martin SK, Thuita-Harun L, Adoyo-Adoyo M, Wasunna KM, 1998. A diagnostic ELISA for visceral leishmaniasis, based on antigen from media conditioned by Leishmania donovani promastigotes. Ann Trop Med Parasitol 92 :571–577.
-
11
Titus RG, Lima G, 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-delayed-type hypersensitivity. J Immunol 133 :1594–1600.
-
12
Lima HC, Bleyenberg J, Titus RG, 1997. A simple method for quantifying Leishmania in tissues of infected animals. Parasitol Today 13 :80–82.
-
13
Stager S, Smith DF, Kaye PM, 2000. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. J Immunol 165 :7064–7071.
-
14
Maryanski JJ, van Snick J, Cerrotini JC, Boon T, 1982. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P 815. III. Clonal analysis of the syngeneic cytolytic T lymphocyte response. Eur J Immunol 12 :401–406.
-
15
Smelt SC, Engwerda CR, McCrossen M, Kaye PM, 1997. Destruction of follicular dendritic cells during chronic visceral leishmaniasis. J Immunol 158 :3813–3821.
-
16
Lainson R, Shaw JJ, 1977. Leishmaniasis in Brazil: XII. Observations on cross-immunity in monkeys and man infected with Leishmania mexicana mexicana, L.m. amazonensis, L. braziliensis braziliensis, L.b. guyanensis and L.b. panamensis. J Trop Med Hyg 80 :29–35.
-
17
Alexander J, Phillips RS, 1978. Leishmania tropica and Leishmania mexicana: cross-immunity in mice. Exp Parasitol 45 :93–100.
-
18
Perez H, Arrendondo B, Machado R, 1979. Leishmania mexicana and Leishmania tropica: cross immunity in C57BL/6 mice. Exp Parasitol 48 :9–14.
-
19
Alexander J, 1988. Sex differences and cross immunity in DBA/2 mice infected with L. mexicana and L. major. Parasitology 96 :297–302.
-
20
Mitchell GF, Handman E, 1987. Heterologous protection in murine cutaneous leishmaniasis. Immunol Cell Biol 65 :387–392.
-
21
Neal RA, Reeves A, Peters W, 1990. Leishmania infecting man and wild animals in Saudi Arabia.7. Partial protection of mice against Leishmania major by prior infection with L. arabica. Trans R Soc Trop Med Hyg 84 :233–238.
-
22
Peters W, Bryceson A, Evans DA, Neal RA, Kaye P, Blackwell J, Killick-Kendrick R, Liew FY, 1990. Leishmania infecting man and wild animals in Saudi Arabia. 8. The influence of prior infection with Leishmania arabica on challenge with L. major in man. Trans R Soc Trop Med Hyg 84 :681–689.
-
23
Melby PC, 1991. Experimental leishmaniasis in human: review. Rev Infect Dis 13 :1009–1017.
-
24
Rachamin N, Jaffe CL, 1993. Pure protein from Leishmania donovani protects mice against both cutaneous and visceral leishmaniasis. J Immunol 150 :2322–2331.
-
25
Gicheru MM, Olobo JO, Anjili CO, 1997. Heterologous protection by Leishmania donovani for Leishmania major infections in the vervet monkey model of the disease. Exp Parasitol 85 :109–116.
-
26
Khalil EA, Hassan AM, Zijlstra EE, Hashim FA, Ibrahim ME, Ghalib HW, Ali MS, 1998. Treatment of visceral leishmaniasis with sodium stibogluconate in Sudan: management of those who do not respond. Ann Trop Med Parasitol 92 :151–158.
-
27
Bebars MA, el Serougi AO, Makled KM, 2000. An experimental vaccine providing heterologous protection for Leishmania species in murine model. J Egypt Soc Parasitol 30 :137–156.
-
28
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.
-
29
Murray HW, Stern JJ, Welte K, Rubin BY, Carriero SM, Nathan CF, 1987. Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with Interleukin 2 and interferon-gamma. J Immunol 138 :2290–2297.
-
30
Goto H, Lindoso LA, 2004. Immunity and immunosuppression in experimental visceral leishmaniasis. Braz J Med Biol Res 37 :615–623.
-
31
De Krey GK, Lima HC, Titus RG, 1998. Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun 66 :827–829.
-
32
Janeway CA, Travers P, Walport M, Shlomchik MJ, 2005. Immunobiology, The Immune System in Health and Disease. New York: Garland, 16.
-
33
Becker I, Salaiza N, Aguirre M, Delgado J, Carrillo-Carrasco N, Kobeh LG, Ruiz A, Cervantes R, Torres AP, Cabrera N, Gonzalez A, Maldonado C, Isisbasi A, 2003. Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2. Mol Biochem Parasitol 130 :65–74.
-
34
De Veer MJ, Curtis JM, Baldwin TM, DiDonato JA, Sexton A, McConville MJ, Handman E, Schofield L, 2003. MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll-like receptor 2 signalling. Eur J Immunol 33 :2822–2831.
-
35
Kropf P, Freudenberg MA, Modolell M, Price HP, Herath S, Antoniazi S, Galanos C, Smith DF, Muller I, 2004. Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major. Infect Immun 72 :1920–1928.
-
36
Flandin JF, Chano F, Descoteaux A, 2006. RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-gamma-primed macrophages. Eur J Immunol 36 :411–420.
-
37
Janeway CA, Travers P, Walport M, Shlomchik MJ, 2005. Immunobiology, The Immune System in Health and Disease. New York: Garland, 37–100.
-
38
Skeiky YA, Coler RN, Brannon M, Stromberg E, Greeson K, Crane RT, Webb JR, Campos-Neto A, Reed SG, 2002. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine 10 :3292–3303.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 192 | 113 | 13 |
| Full Text Views | 477 | 35 | 27 |
| PDF Downloads | 55 | 9 | 0 |
CROSS-PROTECTION AGAINST LEISHMANIA DONOVANI BUT NOT L. BRAZILIENSIS CAUSED BY VACCINATION WITH L. MAJOR SOLUBLE PROMASTIGOTE EXOGENOUS ANTIGENS IN BALB/C MICE
WILLY K. TONUI
WILLY K. TONUI
Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya; Department of Microbiology Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins Colorado
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RICHARD G. TITUS
RICHARD G. TITUS
Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya; Department of Microbiology Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins Colorado
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Vaccinating with soluble Leishmania major promastigote exogenous antigens (LmSEAgs) protects mice against challenge with L. major. To explore the potential of LmSEAgs to cross-protect against infection with other species of Leishmania, BALB/c mice were immunized with LmSEAgs prior to challenge with either L. donovani or L. braziliensis promastigotes. Such mice were protected against L. donovani but not L. braziliensis infection. Leishmania braziliensis–infected mice developed lesions that were not significantly different from those of controls and that contained 13-fold more parasites. In contrast, immunized mice infected with L. donovani were protected as illustrated by low splenic parasite loads (as much as 4,913-fold fewer parasites). This protection corresponded to significant increases in gamma interferon and low production of interleukin-4 (IL-4) IL-4 or IL-10, which suggested an enhanced type 1 response.
Author Notes
- INTRODUCTION
- MATERIALS AND METHODS
- Mice and parasites.
- Preparation of LmSEAgs and immunization of BALB/c mice.
- Infection of mice and determination of parasite numbers in cutaneous lesions or spleens.
- Cell proliferation and cytokine responses of cells from mice immunized with LmSEAgs.
- Cytokine responses post-infection with either L. braziliensis or L. donovani.
- Statistical analyses.
- RESULTS
- Lack of protection of BALB/c mice by vaccination with LmSEAgs against a subsequent challenge with L. braziliensis.
- Reduction of splenic parasite burden by vaccination with LmSEAgs after challenge with L. donovani.
- Proliferation and cytokines before infection.
- Production of elevated levels of type 2 cytokines in LmSEAgs-immunized mice after infection with L. braziliensis.
- Production of elevated levels of type 1 cytokines in LmSEAgs-immunized mice after infection with L. donovani.
- DISCUSSION
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1
World Health Organization, 2006. Leishmaniasis Control Home Page. Available from http://www.who.int/emc/diseases/leish/index.html
-
2
Desjeux P, UNAIDS, 1998. Leishmania and HIV in Gridlock. Geneva: World Health Organization. WHO/CTD/LEISH/98.1 and UNAIDS/98.23.
-
3
Pintado V, Martin-Rabadan P, Rivera ML, Moreno S, Bouza E, 2001. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 80 :54–73.
-
4
Mauel J, 2002. Vaccination against Leishmania infections. Curr Drug Targets Immune Endocr Metabol Disord 2 :201–226.
-
5
Handman E, 2001. Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 14 :229–243.
-
6
Veras P, Brodskyn C, Balestieri F, Freitas L, Ramos A, Queiroz A, Barral A, Beverley S, Barral-Netto M, 1999. A dhfr2ts2 Leishmania major knockout mutant cross-protects against Leishmania amazonensis. Mem Inst Oswaldo Cruz 94 :491–496.
-
7
Lainson R, Bray RS, 1966. Studies on the immunology and serology of leishmaniasis. II. Cross-immunity experiments among different forms of American cutaneous leishmaniasis in monkeys. Trans R Soc Trop Med Hyg 60 :526–532.
-
8
Tonui WK, Mejia JS, Hochberg L, Mbow ML, Ryan JR, Chan AST, Martin SK, Titus RG, 2004. Immunization with Leishmania major exogenous antigens protects susceptible BALB/c mice against challenge infection with L. major. Infect Immun 72 :5654–5661.
-
9
Ryan JR, Smithyman AM, Rajasekariah GH, Hochberg L, Stiteler JM, Martin SK, 2002. Enzyme-linked immunosorbent assay based on soluble promastigote antigen detects immuno-globulin M (IgM) and IgG antibodies in sera from cases of visceral leishmaniasis and cutaneous leishmaniasis. J Clin Microbiol 40 :1037–1043.
-
10
Martin SK, Thuita-Harun L, Adoyo-Adoyo M, Wasunna KM, 1998. A diagnostic ELISA for visceral leishmaniasis, based on antigen from media conditioned by Leishmania donovani promastigotes. Ann Trop Med Parasitol 92 :571–577.
-
11
Titus RG, Lima G, 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-delayed-type hypersensitivity. J Immunol 133 :1594–1600.
-
12
Lima HC, Bleyenberg J, Titus RG, 1997. A simple method for quantifying Leishmania in tissues of infected animals. Parasitol Today 13 :80–82.
-
13
Stager S, Smith DF, Kaye PM, 2000. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. J Immunol 165 :7064–7071.
-
14
Maryanski JJ, van Snick J, Cerrotini JC, Boon T, 1982. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P 815. III. Clonal analysis of the syngeneic cytolytic T lymphocyte response. Eur J Immunol 12 :401–406.
-
15
Smelt SC, Engwerda CR, McCrossen M, Kaye PM, 1997. Destruction of follicular dendritic cells during chronic visceral leishmaniasis. J Immunol 158 :3813–3821.
-
16
Lainson R, Shaw JJ, 1977. Leishmaniasis in Brazil: XII. Observations on cross-immunity in monkeys and man infected with Leishmania mexicana mexicana, L.m. amazonensis, L. braziliensis braziliensis, L.b. guyanensis and L.b. panamensis. J Trop Med Hyg 80 :29–35.
-
17
Alexander J, Phillips RS, 1978. Leishmania tropica and Leishmania mexicana: cross-immunity in mice. Exp Parasitol 45 :93–100.
-
18
Perez H, Arrendondo B, Machado R, 1979. Leishmania mexicana and Leishmania tropica: cross immunity in C57BL/6 mice. Exp Parasitol 48 :9–14.
-
19
Alexander J, 1988. Sex differences and cross immunity in DBA/2 mice infected with L. mexicana and L. major. Parasitology 96 :297–302.
-
20
Mitchell GF, Handman E, 1987. Heterologous protection in murine cutaneous leishmaniasis. Immunol Cell Biol 65 :387–392.
-
21
Neal RA, Reeves A, Peters W, 1990. Leishmania infecting man and wild animals in Saudi Arabia.7. Partial protection of mice against Leishmania major by prior infection with L. arabica. Trans R Soc Trop Med Hyg 84 :233–238.
-
22
Peters W, Bryceson A, Evans DA, Neal RA, Kaye P, Blackwell J, Killick-Kendrick R, Liew FY, 1990. Leishmania infecting man and wild animals in Saudi Arabia. 8. The influence of prior infection with Leishmania arabica on challenge with L. major in man. Trans R Soc Trop Med Hyg 84 :681–689.
-
23
Melby PC, 1991. Experimental leishmaniasis in human: review. Rev Infect Dis 13 :1009–1017.
-
24
Rachamin N, Jaffe CL, 1993. Pure protein from Leishmania donovani protects mice against both cutaneous and visceral leishmaniasis. J Immunol 150 :2322–2331.
-
25
Gicheru MM, Olobo JO, Anjili CO, 1997. Heterologous protection by Leishmania donovani for Leishmania major infections in the vervet monkey model of the disease. Exp Parasitol 85 :109–116.
-
26
Khalil EA, Hassan AM, Zijlstra EE, Hashim FA, Ibrahim ME, Ghalib HW, Ali MS, 1998. Treatment of visceral leishmaniasis with sodium stibogluconate in Sudan: management of those who do not respond. Ann Trop Med Parasitol 92 :151–158.
-
27
Bebars MA, el Serougi AO, Makled KM, 2000. An experimental vaccine providing heterologous protection for Leishmania species in murine model. J Egypt Soc Parasitol 30 :137–156.
-
28
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.
-
29
Murray HW, Stern JJ, Welte K, Rubin BY, Carriero SM, Nathan CF, 1987. Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with Interleukin 2 and interferon-gamma. J Immunol 138 :2290–2297.
-
30
Goto H, Lindoso LA, 2004. Immunity and immunosuppression in experimental visceral leishmaniasis. Braz J Med Biol Res 37 :615–623.
-
31
De Krey GK, Lima HC, Titus RG, 1998. Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun 66 :827–829.
-
32
Janeway CA, Travers P, Walport M, Shlomchik MJ, 2005. Immunobiology, The Immune System in Health and Disease. New York: Garland, 16.
-
33
Becker I, Salaiza N, Aguirre M, Delgado J, Carrillo-Carrasco N, Kobeh LG, Ruiz A, Cervantes R, Torres AP, Cabrera N, Gonzalez A, Maldonado C, Isisbasi A, 2003. Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2. Mol Biochem Parasitol 130 :65–74.
-
34
De Veer MJ, Curtis JM, Baldwin TM, DiDonato JA, Sexton A, McConville MJ, Handman E, Schofield L, 2003. MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll-like receptor 2 signalling. Eur J Immunol 33 :2822–2831.
-
35
Kropf P, Freudenberg MA, Modolell M, Price HP, Herath S, Antoniazi S, Galanos C, Smith DF, Muller I, 2004. Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major. Infect Immun 72 :1920–1928.
-
36
Flandin JF, Chano F, Descoteaux A, 2006. RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-gamma-primed macrophages. Eur J Immunol 36 :411–420.
-
37
Janeway CA, Travers P, Walport M, Shlomchik MJ, 2005. Immunobiology, The Immune System in Health and Disease. New York: Garland, 37–100.
-
38
Skeiky YA, Coler RN, Brannon M, Stromberg E, Greeson K, Crane RT, Webb JR, Campos-Neto A, Reed SG, 2002. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine 10 :3292–3303.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 192 | 113 | 13 |
| Full Text Views | 477 | 35 | 27 |
| PDF Downloads | 55 | 9 | 0 |