Skip to main content

Advertisement

SpringerLink
Log in

Leishmania major infection in susceptible and resistant mice elicit a differential humoral response against a total soluble fraction and defined recombinant antigens of the parasite

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

In the present work, we analyzed the humoral response of Leishmania major experimentally infected BALB/c and C57BL/6 mice against three Leishmania antigens: total soluble antigen (soluble leishmania antigen(SLA)), a chimerical recombinant protein formed by the genetic fusion of four cytoplasmic proteins (PQ), and a kinetoplastic membrane protein (Kmp-11). We determined the correlation between the immune response against these proteins and the histopathological changes induced in the susceptible and resistant mice after infection. The data showed the existence of wide differences in the recognition of SLA, PQ, and Kmp-11 by the sera from both strains. The anti-SLA titer of BALB/c was 100 times higher than that of C57BL/6 mice. Antibodies against the recombinant Kmp-11 were detected only in infected BALB/c during the first stage of the infection. In contrast, the PQ protein was recognized by the sera from infected BALB/c mice but exclusively when they were in a late-lesion period. The data suggest that the response against the membrane Kmp-11 protein is transient and correlates with early developmental stages of the infection, whereas the response against cytoplasmic proteins as those present in PQ is sustained and could be considered as a marker of an advanced stage of the infection and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Andrade ZA, Reed ST, Roters SB, Sadigursky M (1984) Patogenia da leishmaniose cutânea experimental a importância da necrose na eliminaçâo dos parasitos das lesŏes. Rev Soc Bras Med Trop 17:187–197

    Google Scholar 

  • Beil WJ, Meinardus-Hager G, Neugebauer DC, Sorg C (1992) Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J Leukoc Biol 52:135–142

    PubMed  CAS  Google Scholar 

  • Berberich C, Requena JM, Alonso C (1997) Cloning of genes and expression and antigenicity analysis of the Leishmania infantum KMP11 protein. Exp Parasitol 85(1):105–108

    Article  PubMed  CAS  Google Scholar 

  • Chang KP, Reed SG, McGwire BS, Soong L (2003) Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity. Acta Trop 85(3):375–390

    Article  PubMed  Google Scholar 

  • De Carvalho LP, Soto M, Jeronimo S, Dondji B, Bacellar O, Luz V, Orge Orge G, Alonso C, Jesus AR, Carvalho EM (2003) Characterization of the immune response to Leishmania infantum recombinant antigens. Microbes Infect 5(1):7–12

    Article  PubMed  Google Scholar 

  • Deplazes P, Smith NC, Arnold P, Lutz H, Eckert J (1995) Specific IgG1 and IgG2 antibody responses of dogs to Leishmania infantum and other parasites. Parasite Immunol 17(9):451–458

    Article  PubMed  CAS  Google Scholar 

  • Ghose AC, Haldar JP, Pal SC, Mishra BP, Mishra KK (1980) Serological investigations of Indian kala-azar. Clin Exp Immunol 40(2):318–326

    PubMed  CAS  Google Scholar 

  • Gonzalo RM, Rodríguez JR, Rodríguez D, González-Aseguinolaza G, Larraga V, Esteban M (2001) Protective immune response against cutaneous leishmaniasis by prime/booster immunization regimens with vaccinia virus recombinants expressing Leishmania infantum p36/LACK and IL-12 in combination with purified p36. Microbes Infect 3(9):701–710

    Article  PubMed  CAS  Google Scholar 

  • Heinzel FP, Sadick MD, Mutha SS, Locksley RM (1991) Production of interferon gamma, interleukin-2, interleukin-4 and interleukin-10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci U S A 88(16):7011–7015

    Article  PubMed  CAS  Google Scholar 

  • Howard MK (1985) Host immunity to leishmaniasis. In: Bray RS, Chang KP (eds) Human parasitic diseases, vol. I: leishmaniasis. Elsevier, Amsterdam, pp 139–162

    Google Scholar 

  • Iniesta V, Carcelén J, Molano I, Peixoto PMV, Redondo E, Parra P, Mangas M, Monroy M, Gómez Nieto C, Corraliza I (2005) Arginase I induction during Leishmania major infection is mediating the development of the disease. Infect Immun 73(9):6085–6090

    Article  PubMed  CAS  Google Scholar 

  • Joshi PB, Kelly BL, Kamhawi S, Sacks DL, McMaster WR (2002) Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol 120:33–40

    Article  PubMed  CAS  Google Scholar 

  • Liew FY, O’Donnell CA (1993) Immunology of leishmaniasis. Adv Parasitol 32:161–259

    Article  PubMed  CAS  Google Scholar 

  • Locksley RM, Heinzel FP, Holaday BJ, Mutha SS, Reiner SL, Sadick MD (1991) Induction of Th1 and Th2 CD4+ subsets during murine Leishmania major infection. Res Immunol 142(1):28–32

    Article  PubMed  CAS  Google Scholar 

  • Molano I, Alonso MG, Mirón C, Redondo E, Requena JM, Soto M, Gómez Nieto C, Alonso C (2003) A Leishmania infantum multi-component antigenic protein mixed with live BCG confers protection to dogs experimentally infected with L. infantum. Vet Immunol Immunopathol 92(1–2):1–13

    Article  PubMed  CAS  Google Scholar 

  • Monroy A, Ridley DS, Heather CJ, Ridley MJ (1980) Histological studies of the elimination of Leishmania enriettii from skin lesions in the guinea-pig. Br J Exp Pathol 61(6):601–610

    PubMed  CAS  Google Scholar 

  • Morsy TA, El-Okby LM, Helmy OM, Makrm SS, Essa MH (1987) The class of immunoglobulins versus the histological picture in cutaneous leishmaniasis. J Egypt Soc Parasitol 17(2):723–728

    PubMed  CAS  Google Scholar 

  • Nieto CG, García-Alonso M, Requena JM, Mirón C, Soto M, Alonso C, Navarrete I (1999) Analysis of the humoral immune response against total and recombinant antigens of Leishmania infantum: correlation with disease progression in canine experimental leishmaniosis. Vet Immunol Immunopathol 67(2):117–130

    Article  PubMed  CAS  Google Scholar 

  • Requena JM, Alonso C, Soto M (2000a) Evolutionarily conserved proteins as prominent immunogens during Leishmania infections. Parasitol Today 16(6):246–250

    Article  PubMed  CAS  Google Scholar 

  • Requena JM, Soto M, Doria MD, Alonso C (2000b) Immune and clinical parameters associated with Leishmania infantum infection in the golden hamster model. Vet Immunol Immunopathol 76(3–4):269–281

    Article  PubMed  CAS  Google Scholar 

  • Ridley MJ, Ridley DS (1984) Cutaneous leishmaniasis: immune complex formation and necrosis in the acute phase. Br J Exp Pathol 65(3):327–336

    PubMed  CAS  Google Scholar 

  • Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2(11):845–858

    Article  PubMed  CAS  Google Scholar 

  • Satoskar AR, Stamn LM, Zhang X, Satoskar AA, Okano M, Terhorst C, David JR, Wang B (1999) Mice lacking NK cells develop an efficient Th1 response and control cutaneous Leishmania major infection. J Immunol 162(11):6747–6754

    PubMed  CAS  Google Scholar 

  • Scott P, Natovitz P, Coffman RL, Pearce E, Sher A (1988) Immunoregulation of cutaneous leishmaniasis T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med 168(5):1675–1684

    Article  PubMed  CAS  Google Scholar 

  • Solbach W, Asmuss PA, Zimmermann S, Humborg C, Rollinghoff M (1995) Protective effect of leflunomide on the natural course of Leishmania major-induced disease in genetically susceptible BALB/c mice. Int J Immunopharmacol 17(6):481–488

    Article  PubMed  CAS  Google Scholar 

  • Soto M, Requena JM, Quijada L, Garcia M, Guzman F, Patarroyo ME, Alonso C (1995a) Mapping of the linear antigenic determinants from the Leishmania infantum histone H2A recognized by sera from dogs with leishmaniasis. Immunol Lett 48(3):209–214

    Article  PubMed  CAS  Google Scholar 

  • Soto M, Requena JM, Quijada L, Angel SO, Gomez LC, Guzman F, Patarroyo ME, Alonso C (1995b) During active viscerocutaneous leishmaniasis the anti-P2 humoral response is specifically triggered by the parasite P proteins. Clin Exp Immunol 100(2):246–252

    Article  PubMed  CAS  Google Scholar 

  • Soto M, Requena JM, Quijada L, Alonso C (1998) Multicomponent chimeric antigen for serodiagnosis of canine visceral leishmaniasis. J Clin Microbiol 36(1):58–63

    PubMed  CAS  Google Scholar 

  • Spath GF, Epstein L, Leader B, Singer SM, Avila HA, Turco SJ, Beverley SM (2000) Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major. Proc Natl Acad Sci U S A 97(16):9258–9263

    Article  PubMed  CAS  Google Scholar 

  • Stacey KJ, Blackwell J (1999) Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major. Infect Immun 67(8):3719–3726

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grant BIO2002-04049-C02-02 from Centro de Investigación Científica y Tecnológica (Spain).

The experiments have been performed according to the Spanish current laws about care and protection of animals for researching purposes.

Author information

Authors and Affiliations

  1. Unidad de Parasitología y Enfermedades Parasitarias, Universidad de Extremadura, Avda. de la Universidad s/n, 10.071, Cáceres, Spain

    Virginia Iniesta, Jesualdo Carcelén, Javier Fernández-Cotrina & Carlos Gómez Nieto

  2. Departamento de Bioquímica y Biología Molecular, Universidad de Extremadura, Avda. de la Universidad s/n, 10.071, Cáceres, Spain

    Inés Corraliza

  3. Unidad de Anatomía Patológica, Universidad de Extremadura, Avda. de la Universidad s/n, 10.071, Cáceres, Spain

    Luis Gómez Gordo

  4. Unidad de Genética, Facultad de Veterinaria, Universidad de Extremadura, Avda. de la Universidad s/n, 10.071, Cáceres, Spain

    Juan Carlos Parejo

  5. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Cantoblanco, 28049, Madrid, Spain

    Javier Carrión, Manuel Soto & Carlos Alonso

  6. Unidad de Parasitología y Enfermedades Parasitarias, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Extremadura, Avda. de la Universidad s/n 10.071, Cáceres, Spain

    Virginia Iniesta

Authors
  1. Virginia Iniesta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inés Corraliza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jesualdo Carcelén
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luis Gómez Gordo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Javier Fernández-Cotrina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juan Carlos Parejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier Carrión
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manuel Soto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carlos Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carlos Gómez Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Virginia Iniesta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iniesta, V., Corraliza, I., Carcelén, J. et al. Leishmania major infection in susceptible and resistant mice elicit a differential humoral response against a total soluble fraction and defined recombinant antigens of the parasite. Parasitol Res 102, 887–893 (2008). https://doi.org/10.1007/s00436-007-0844-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-007-0844-9

Keywords

Search

Navigation