AJTMH Transactions of the Royal Society of Tropical Medicine and Hygiene
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am. J. Trop. Med. Hyg., 71(4), 2004, pp. 407-411
Copyright © 2004 by The American Society of Tropical Medicine and Hygiene

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (8)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by VANLOUBBEECK, Y.
Right arrow Articles by JONES, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by VANLOUBBEECK, Y.
Right arrow Articles by JONES, D. E.
Related Collections
Right arrow Immunology
Right arrow Leishmaniasis

PROTECTION OF C3HEB/FEJ MICE AGAINST LEISHMANIA AMAZONENSIS CHALLENGE AFTER PREVIOUS LEISHMANIA MAJOR INFECTION

YANNICK VANLOUBBEECK AND DOUGLAS E. JONES
Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The Th1 response elicited in mice infected with Leishmania major has been used as a model to characterize cellular immune defects associated with L. amazonensis infection. However, it is not known if the immune response associated with the infection by virulent L. major parasites can promote resistance to a subsequent L. amazonensis infection. Our data demonstrate that C3HeB/FeJ mice infected subcutaneously with virulent L. major are resistant to an L. amazonensis challenge. The healing phenotype is characterized by a Th1 response as measured by increased production of interferon-{gamma} and low levels of interleukin-4 in the draining lymph node. Together, this indicates that the Th1 response associated with L. major infection can promote resistance to L. amazonensis infection and that it can be used as a tool to study the immune defects associated with L. amazonensis infection.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania, which are transmitted to the host through the bite of an infected sand fly. The disease is characterized by a variety of clinical manifestations, depending on the Leishmania species involved and the type of immune response mounted by the host.1,2 Leishmania major and L. amazonensis are both associated with the cutaneous form of the disease: the lesions induced by L. major are typically localized and self-healing, while the ones caused by L. amazonensis can become diffuse and chronic, sometimes affecting mucous membranes.1,3 Mouse models of leishmaniasis have helped to uncover some of the immune factors involved with resistance and susceptibility to the disease. For example, while C3H and C57BL/6 mice are resistant to L. major, they are susceptible to L. amazonensis. Resistance and susceptibility to L. major are mediated by Th1 and Th2 immune responses, respectively.4 The susceptibility to L. amazonensis is thought to result from an inability to mount a Th1 response.5–9 In particular, it has been shown that the CD4+ T cells from L. amazonensis-infected mice have defective expression of several cytokine and chemokine receptors in comparison to the CD4+ T cells from L. major-infected mice.6,9 However, while the immune response to L. major infection is used as a model in this experimental system of murine cutaneous leishmaniasis, it is not known if the Th1 response elicited by L. major in vivo would provide protection to a subsequent L. amazonensis infection. In fact, it has been reported that even after exogenous administration of interleukin-12 (IL-12) or in the absence IL-10 or IL-4, mice still develop chronic cutaneous lesions upon L. amazonensis infection.6,7,9,10 However, in mouse studies using L. major, the administration of IL-12 or antibody to IL-4, or the absence of IL-10 was associated with disease control.11–14 Therefore, it is possible that the immune response necessary to promote resistance to L. amazonensis may not be the same as that for L. major.

Cross-protection between different Leishmania species using either Leishmania antigens, attenuated parasites, or live Leishmania promastigotes have been previously described in mice,15–30 monkeys,31–33 and humans.32,34 However, the effectiveness of cross-protection reported in the literature is variable and several studies have reported its failure, depending on the experimental design and/or the Leishmania spp. involved.15,17,20,32,34,35 Furthermore, the cross-protection induced in mice by a previous Leishmania infection does not necessarily correlate with complete healing. In contrast, it is sometimes associated with the persistence of a smaller lesion or even a slower progressing lesion than the control mice.18,21,29 Finally, the route of immunization appears to have an influence on the subsequent protection, and subcutaneous immunization has provided variable degrees of resistance.18,25 In particular, one mouse study has reported efficient protection to L. amazonensis after a subcutaneous infection with an avirulent strain of L. major.25 However, the study did not characterize the associated immune response nor was parasite quantification determined.

Our data indicate that the Th1 response developed by C3HeB/FeJ mice after infection with wild-type L. major promastigotes does promote resistance to a L. amazonensis challenge, as determined by the development of a transient lesion and decreased parasite load. To our knowledge, the present report is the first to determine the effectiveness of cross-protection using an infectious challenge composed of as much as 5 x 106 L. amazonensis promastigotes and using the subcutaneous route of immunization. Our data also confirm that the immune response associated with L. major infection is a good model for the study of the immune defects associated with L. amazonensis infection.


MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Parasites. Culture of L. amazonensis (MHOM/BR/00/ LTB0016) or L. major (MHOM/IL/80/Friedlin) parasites and the preparation of parasite antigen were performed as previously described.7 Parasite quantification was determined when the mice had healed their L. amazonensis infection, i.e., 10–12 weeks post-L. amazonensis challenge. For the parasite quantification from cutaneous lesions, the infected feet were disinfected with 70% ethanol and the skin was dissected away. The remaining subcutaneous lesion was homogenized using a Tenbrock tissue homogenizer (Kontes, Vineland, NJ), washed twice in phosphate-buffered saline, and resuspended in 2 mL of Grace’s insect cell culture medium (Life Technologies, Grand Island, NY) supplemented with 20% heat-inactivated fetal bovine serum, 2 mM glutamine, 100 units/mL of penicillin, and 100 µg/mL of streptomycin. A 10-fold serial dilution of each parasite suspension was then performed in triplicate and incubated at 27°C for eight days before parasite quantification was assessed. The lower detection limit of our quantification assay was 102 parasites per foot, and when parasite numbers were lower than the detection limit a value of 10 was given to the sample.

Mice. C3HeB/FeJ mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and bred in a specific pathogen-free facility. The Committee on Animal Care at Iowa State University approved all protocols involving animals. Five- to eight-week-old mice (3–6 mice per group) were inoculated subcutaneously with 5 x 106 stationary phase L. major promastigotes in their left hindfoot. Eleven to fifteen weeks later, when mice have healed their primary L. major infection, the mice were infected subcutaneously with 5 x 106 stationary phase L. amazonensis promastigotes in their right hind footpad. Lesion size of the footpads was monitored weekly with a dial micrometer (L.S. Starrett Co., Athol, MA), and the results were expressed as the difference between the thickness of the right and left hind footpads. After infection with L. amazonensis, the thickness of the left feet (those that had healed a previous L. major infection) remained stable.

Recall responses. The cells from the popliteal lymph node draining the L. amazonensis-infected feet were obtained 10–12 weeks after L. amazonensis infection and recall responses were obtained as previously described.7 The cells were incubated with medium containing 50 µg of L. amazonensis antigen/mL with or without 1 ng/mL of recombinant murine IL-12 (PeproTech Inc., Rocky Hill, NJ). Supernatants were harvested after 72 hours, and interferon-{gamma} (IFN-{gamma}) and IL-4 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Recombinant IFN-{gamma} (Pharmingen, San Diego, CA) and IL-4 (PeproTech Inc.) were used on each ELISA plate to set up a standard curve. The sensitivity of the IFN-{gamma} ELISA ranged between 39 and 78 pg/mL; the sensitivity of the IL-4 ELISA was 39 pg/mL. All ELISAs were performed with commercially available antibodies (Pharmingen), peroxidase-conjugated streptavidin (Jackson ImmunoResearch Laboratories, West Grove, PA) and 2, 2'-azino-di(3-ethylbenzthiazoline-6-sulfonate) (ABTS) microwell peroxidase substrate (Kirkegaard and Perry Laboratories, Gaithersburg, MD) following the manufacturer instructions.


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Resistance of mice infected with L. major to a subsequent L. amazonensis infection. The C3HeB/FeJ mice were infected subcutaneously in their left hind footpad with 5 x 106 L. major stationary phase promastigotes. The resulting lesion consisted of a discrete cutaneous nodule that occasionally ulcerated and consistently healed over the following 11–15 weeks. At these time points, the mice were re-infected subcutaneously with 5 x 106 L. amazonensis stationary phase promastigotes in their right hind footpad and the associated lesion size was measured weekly. As a control, naive mice were also infected with 5 x 106 L. amazonensis stationary phase promastigotes in their right hindfoot. As shown in Figure 1Go, control mice infected with L. amazonensis developed chronic lesions, whereas in mice previously infected with L. major, the L. amazonensis lesion was transient and healed in 10–12 weeks. The chronic lesion of L. amazonensis-infected mice contained an average of 107 parasites (Figure 2Go). In contrast, the healing response of mice infected with L. major and subsequently with L. amazonensis was associated with a significant decrease in parasite load (Figure 2Go).



View larger version (17K):
[in this window]
[in a new window]
  		    FIGURE 1. Protection provided by a previous infection with Leish-mania major to a subsequent infectious challenge with L. amazonensis. C3HeB/FeJ mice were infected with 5 x 106 L. major stationary phase promastigotes in the left hind footpad. When the mice had healed their L. major infection, they were re-infected with 5 x 106 stationary phase L. amazonensis promastigotes in their right hind footpad, as described in the Materials and Methods. The lesion size of the L. amazonensis-infected feet was measured over time after the re-infection. Mice sequentially infected with L. major and then L. amazonensis (Lm - La) developed transient lesions in comparison to L. amazonensis-infected control mice (La control). The values shown are the mean ± SD from one experiment (five mice per group) representative of five independent experiments.

 


View larger version (10K):
[in this window]
[in a new window]
  		    FIGURE 2. Significant decrease in parasite load of mice sequentially infected with Leishmania major and then L. amazonensis (Lm - La). The number of parasites within the L. amazonensis-infected feet of Lm - La mice or L. amazonensis-infected controls (La control) was determined 10-12 weeks after L. amazonensis infection. * indicates a statistically significant difference (P < 0.05, by t-test). The values shown are pooled from five independent experiments and expressed as the mean ± SEM.

 
Association of resistance to L. amazonensis infection with an enhanced Th1 response within the draining lymph node. In each experiment, the mice were killed 10–12 weeks after L. amazonensis infection, a time at which the associated cutaneous lesion had resolved. The cells from the draining lymph node were cultured in a three-day recall response with or without L. amazonensis antigens and the levels of IL-4 and IFN-{gamma} were determined in the culture supernatants. While lymph node cells from both groups of mice produced low to undetectable amounts of IL-4, mice sequentially infected with L. major and L. amazonensis produced significantly higher levels of IFN-{gamma} than the L. amazonensis-infected control mice (Figure 3AGo). The levels of IFN-{gamma} detected were similar whether L. amazonensis or L. major antigens were present during the three-day recall response (mean ± SEM = 4.5 ± 1.0 ng/mL and 5.9 ± 1.5 ng/mL with L. amazonensis and L. major antigens, respectively). To further determine the phenotype of the healing immune response, we also determined the IL-12 responsiveness of the cells from the draining lymph node by measuring the levels of IFN-{gamma} produced in vitro in response to L. amazonensis antigen and recombinant murine IL-12. The IL-12 responsiveness is a marker of Th1 responses and as shown in Figure 3BGo, draining lymph node cells from mice sequentially infected with L. major and L. amazonensis produced significantly more IFN-{gamma} than the L. amazonensis-infected control in response to IL-12. These data indicate that the healing phenotype observed in co-infected mice is associated with an increased Th1 response at the level of the draining lymph node.



View larger version (10K):
[in this window]
[in a new window]
  		    FIGURE 3. Th1 cytokine profile within the draining lymph node (DLN) of mice sequentially infected with Leishmania major and L. amazonensis (Lm - La). Mice were infected as described in the Materials and Methods. Ten to twelve weeks post-L. amazonensis infection, DLN cells were plated in vitro with L. amazonensis antigens with or without interleukin-12 (IL-12) for three days and the total amounts of interferon-{gamma} (IFN-{gamma}) and IL-4 were measured in the culture supernatants. A, Both L. amazonensis-infected control mice (La control) and Lm - La mice produced low to undetectable levels of IL-4. However, Lm - La mice produced significantly more IFN-{gamma} than control mice. * indicates a statistically significant difference (P < 0.05, by t-test). B, When IL-12 was added to the in vitro cell cultures, DLN cells from Lm - La mice produced more IFN-{gamma} than La control mice. The values shown are pooled from five independent experiments and expressed as the mean ± SEM. Ag = antigen.

 

DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The Th1 immune response elicited after L. major infection has been used as a model to describe T cell defects associated with L. amazonensis infection.6,9 However, whether the immune response of L. major-infected mice represents an appropriate model to study L. amazonensis infection, i.e., if the Th1 response of mice infected with virulent L. major would promote resistance to a subsequent L. amazonensis infection, is not known. Our data indicate that mice previously infected with virulent L. major were able to control a L. amazonensis infection, characterized by lesion resolution and a decreased parasite load (Figures 1Go and 2Go). The healing phenotype was associated with a Th1 response as determined by low levels of IL-4 and high levels of IFN-{gamma} in the in vitro recall response from the draining lymph node (Figure 3AGo). This is consistent with previous studies in which the vaccination of mice with parasite antigen or DNA, with or without an adjuvant, was shown to promote resistance to L. amazonensis infection.24,27–29,36–38 When determined, the healing response following vaccination correlated with increased production of IFN-{gamma} in the draining lymph node, the spleen, or at the lesion site.24,27–29,37 Furthermore, the adoptive transfer of L. amazonensis-specific Th1 cells into C3H mice was recently shown to promote resistance to subsequent L. amazonensis infection.9 Altogether, this demonstrates that resistance to L. amazonensis infection can be associated with a Th1 response. The IL-12 responsiveness is another marker of Th1 responses that was reported to correlate with the potential of mice to heal Leishmania infection.39–41 Therefore, the increased IL-12 responsiveness of draining lymph node cells from mice with L. major and subsequently with L. amazonensis further supports the Th1 phenotype of their healing response (Figure 3BGo).

Previous studies have shown that the exogenous administration of the Th1 cytokines IL-12 or IFN-{gamma} was not able to promote resistance to L. amazonensis.6,42 In addition, the neutralization or the absence of IL-4 or IL-10, respectively could not restore resistance to L. amazonensis.6,7,9,10 Altogether, this suggests that these cytokines are not, by themselves, altering the course of L. amazonensis infection. Rather, resistance may require an array of immune factors that the L. major-induced immune response, as a whole, can provide. This would also suggest that some elements of a parasite-specific immune response may be needed prior the L. amazonensis challenge to provide protection. Our data confirm that the immune factors necessary to promote resistance to L. amazonensis are present after a L. major infection. Finally, our data also support a previous study suggesting that subcutaneous vaccination may be effective in promoting resistance to L. amazonensis infection,25 even in an experimental system using a high dose challenge.

In conclusion, our data show that the Th1 response of C3HeB/FeJ mice infected with L. major is able to promote protection to a subsequent L. amazonensis challenge. Although leishmanization, i.e., the inoculation of virulent Leishmania promastigotes as a vaccine, has been currently abandoned, this co-infection model confirms that the immune response developed after L. major infection is a good model to study the defects associated with L. amazonensis infection. This model will allow us to better understand and define the immune factors necessary or sufficient to promote resistance to L. amazonensis.

Received December 12, 2003. Accepted for publication June 3, 2004.

Acknowledgments: We thank Dennis Byrne for technical assistance.

Financial support: This work was supported by National Institutes of Health grant AI-48357 and the Biotechnology Council and College of Veterinary Medicine at Iowa State University. Yannick Vanloubbeeck was supported by a Van Roekel scholarship.

Authors’ address: Yannick Vanloubbeeck and Douglas E. Jones, Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, Telephone: 515-294-3282. Fax: 515-294-5423, E-mails: yannick{at}iastate.edu and jonesdou{at}iastate.edu.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Grevelink SA, Lerner EA, 1996. Leishmaniasis. J Am Acad Dermatol 34: 257–272.[ISI][Medline]
  2. Marsella R, Ruiz de Gopegui R, 1998. Leishmaniasis: a re-emerging zoonosis. Int J Dermatol 37: 801–814.[ISI][Medline]
  3. Barral A, Pedral-Sampaio D, Grimaldi G Jr, Momen H, McMahon-Pratt D, Ribeiro de Jesus A, Almeida R, Badaro R, Barral-Netto M, Carvalho EM, Johnson WD Jr, 1991. Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am J Trop Med Hyg 44: 536–546.
  4. Sacks D, Noben-Trauth N, 2002. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2: 845–858.[ISI][Medline]
  5. Afonso LC, Scott P, 1993. Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. Infect Immun 61: 2952–2959.[Abstract/Free Full Text]
  6. Jones DE, Buxbaum LU, Scott P, 2000. IL-4-independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. J Immunol 165: 364–372.[Abstract/Free Full Text]
  7. Jones DE, Ackermann MR, Wille U, Hunter CA, Scott P, 2002. Early enhanced Th1 response after Leishmania amazonensis infection of C57BL/6 interleukin-10-deficient mice does not lead to resolution of infection. Infect Immun 70: 2151–2158.[Abstract/Free Full Text]
  8. Soong L, Chang CH, Sun J, Longley BJ Jr, Ruddle NH, Flavell RA, McMahon-Pratt D, 1997. Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. J Immunol 158: 5374–5383.[Abstract]
  9. Ji J, Sun J, Soong L, 2003. Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis. Infect Immun 71: 4278–4288.[Abstract/Free Full Text]
  10. Padigel UM, Alexander J, Farrell JP, 2003. The role of interleukin-10 in susceptibility of BALB/c mice to infection with Leishmania mexicana and Leishmania amazonensis. J Immunol 171: 3705–3710.[Abstract/Free Full Text]
  11. Heinzel FP, Schoenhaut DS, Rerko RM, Rosser LE, Gately MK, 1993. Recombinant interleukin 12 cures mice infected with Leishmania major. J Exp Med 177: 1505–1509.[Abstract/Free Full Text]
  12. Kane MM, Mosser DM, 2001. The role of IL-10 in promoting disease progression in leishmaniasis. J Immunol 166: 1141–1147.[Abstract/Free Full Text]
  13. Sadick MD, Heinzel FP, Holaday BJ, Pu RT, Dawkins RS, Locksley RM, 1990. Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med 171: 115–127.[Abstract/Free Full Text]
  14. Chatelain R, Varkila K, Coffman RL, 1992. IL-4 induces a Th2 response in Leishmania major-infected mice. J Immunol 148: 1182–1187.[Abstract]
  15. Alexander J, Phillips RS, 1978. Leishmania tropica and Leishmania mexicana: cross-immunity in mice. Exp Parasitol 45: 93–100.[ISI][Medline]
  16. Perez H, Arredondo B, Machado R, 1979. Leishmania mexicana and Leishmania tropica: cross immunity in C57BL/6 mice. Exp Parasitol 48: 9–14.[ISI][Medline]
  17. Alexander J, 1982. A radioattenuated Leishmania major vaccine markedly increases the resistance of CBA mice to subsequent infection with Leishmania mexicana mexicana. Trans R Soc Trop Med Hyg 76: 646–649.[ISI][Medline]
  18. Howard JG, Nicklin S, Hale C, Liew FY, 1982. Prophylactic immunization against experimental leishmaniasis: I. Protection induced in mice genetically vulnerable to fatal Leishmania tropica infection. J Immunol 129: 2206–2212.[ISI][Medline]
  19. Howard JG, Liew FY, Hale C, Nicklin S, 1984. Prophylactic immunization against experimental leishmaniasis. II. Further characterization of the protective immunity against fatal Leishmania tropica infection induced by irradiated promastigotes. J Immunol 132: 450–455.[Abstract]
  20. Alexander J, Kaye PM, 1985. Immunoregulatory pathways in murine leishmaniasis: different regulatory control during Leishmania mexicana mexicana and Leishmania major infections. Clin Exp Immunol 61: 674–682.[ISI][Medline]
  21. Frommel D, Ogunkolade BW, Vouldoukis I, Monjour L, 1988. Vaccine-induced immunity against cutaneous leishmaniasis in BALB/c mice. Infect Immun 56: 843–848.[Abstract/Free Full Text]
  22. Mitchell GF, Handman E, 1987. Heterologous protection in murine cutaneous leishmaniasis. Immunol Cell Biol 65: 387–392.
  23. 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.[ISI][Medline]
  24. Soong L, Duboise SM, Kima P, McMahon-Pratt D, 1995. Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infect Immun 63: 3559–3566.[Abstract]
  25. Veras P, Brodskyn C, Balestieri F, Freitas L, Ramos A, Queiroz A, Barral A, Beverley S, Barral-Netto M, 1999. A dhfrts-Leishmania major knockout mutant cross-protects against Leishmania amazonensis. Mem Inst Oswaldo Cruz 94: 491–496.[ISI][Medline]
  26. 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 murine model. J Egypt Soc Parasitol 30: 137–156.[Medline]
  27. Campbell K, Diao H, Ji J, Soong L, 2003. DNA immunization with the gene encoding P4 nuclease of Leishmania amazonensis protects mice against cutaneous Leishmaniasis. Infect Immun 71: 6270–6278.[Abstract/Free Full Text]
  28. Colmenares M, Kima PE, Samoff E, Soong L, McMahon-Pratt D, 2003. Perforin and gamma interferon are critical CD8+ T-cell-mediated responses in vaccine-induced immunity against Leishmania amazonensis infection. Infect Immun 71: 3172–3182.[Abstract/Free Full Text]
  29. Pinto EF, de Mello Cortezia M, Rossi-Bergmann B, 2003. Interferon-gamma-inducing oral vaccination with Leishmania amazonensis antigens protects BALB/c and C57BL/6 mice against cutaneous leishmaniasis. Vaccine 21: 3534–3541.[ISI][Medline]
  30. Coelho EA, Tavares CA, Carvalho FA, Chaves KF, Teixeira KN, Rodrigues RC, Charest H, Matlashewski G, Gazzinelli RT, Fernandes AP, 2003. Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection. Infect Immun 71:3988–3994.[Abstract/Free Full Text]
  31. 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.[ISI][Medline]
  32. 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.[ISI][Medline]
  33. 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.[ISI][Medline]
  34. Lainson R, Shaw JJ, 1966. Studies on the immunology and serology of leishmaniasis. 3. on the cross-immunity between Panamanian cutaneous leishmaniasis and Leishmania mexicana infection in man. Trans R Soc Trop Med Hyg 60: 533–535.[ISI][Medline]
  35. 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.[ISI][Medline]
  36. Champsi J, McMahon-Pratt D, 1988. Membrane glycoprotein M-2 protects against Leishmania amazonensis infection. Infect Immun 56: 3272–3279.[Abstract/Free Full Text]
  37. Beyrodt CG, Pinto AR, Freymuller E, Barbieri CL, 1997. Characterization of an antigen from Leishmania amazonensis amastigotes able to elicit protective responses in a murine model. Infect Immun 65: 2052–2059.[Abstract]
  38. Chen G, Darrah PA, Mosser DM, 2001. Vaccination against the intracellular pathogens Leishmania major and L. amazonensis by directing CD40 ligand to macrophages. Infect Immun 69: 3255–3263.[Abstract/Free Full Text]
  39. Jones D, Elloso MM, Showe L, Williams D, Trinchieri G, Scott P, 1998. Differential regulation of the interleukin-12 receptor during the innate immune response to Leishmania major. Infect Immun 66: 3818–3824.[Abstract/Free Full Text]
  40. Himmelrich H, Parra-Lopez C, Tacchini-Cottier F, Louis JA, Launois P, 1998. The IL-4 rapidly produced in BALB/c mice after infection with Leishmania major down-regulates IL-12 receptor beta 2-chain expression on CD4+ T cells resulting in a state of unresponsiveness to IL-12. J Immunol 161: 6156–6163.[Abstract/Free Full Text]
  41. Hondowicz BD, Park AY, Elloso MM, Scott P, 2000. Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania major-infected mice. Eur J Immunol 30: 2007–2014.[ISI][Medline]
  42. Barral-Netto M, Von Sohsten RL, Teixeira M, dos Santos WL, Pompeu ML, Moreira RA, Oliveira JT, Cavada BS, Falcoff E, Barral A, 1996. In vivo protective effect of the lectin from Canavalia brasiliensis on BALB/c mice infected by Leishmania amazonensis. Acta Trop 60: 237–250.[ISI][Medline]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. C. Hsu and P. Scott
Leishmania mexicana Infection Induces Impaired Lymph Node Expansion and Th1 Cell Differentiation Despite Normal T Cell Proliferation
J. Immunol., December 15, 2007; 179(12): 8200 - 8207.
[Abstract] [Full Text] [PDF]

Home page
 Am J Trop Med HygHome page
R. M. MUKBEL, C. PATTEN JR., K. GIBSON, M. GHOSH, C. PETERSEN, and D. E. JONES
MACROPHAGE KILLING OF LEISHMANIA AMAZONENSIS AMASTIGOTES REQUIRES BOTH NITRIC OXIDE AND SUPEROXIDE
Am J Trop Med Hyg, April 1, 2007; 76(4): 669 - 675.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. H. Serezani, J. H. Perrela, M. Russo, M. Peters-Golden, and S. Jancar
Leukotrienes Are Essential for the Control of Leishmania amazonensis Infection and Contribute to Strain Variation in Susceptibility.
J. Immunol., September 1, 2006; 177(5): 3201 - 3208.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (8)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by VANLOUBBEECK, Y.
Right arrow Articles by JONES, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by VANLOUBBEECK, Y.
Right arrow Articles by JONES, D. E.
Related Collections
Right arrow Immunology
Right arrow Leishmaniasis

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS