Immune and clinical parameters associated with Leishmania infantum infection in the golden hamster model.

For experimental infections with viscerotropic strains of Leishmania, a suitable animal model is not yet defined. In the present work, we have reappraised the use of golden hamster (Mesocricetus auratus) as an experimental model for infection with Leishmania infantum. Groups of hamsters were challenged by the intracardial route with doses ranging from 10(3) to 10(5) infectious promastigotes and the animals were monitored for 1-year follow-up period. The outcome of the infection was assessed by clinical symptoms of leishmaniasis, parasite loads in both liver and spleen, humoral response to Leishmania antigens and antibody levels in kidneys. The humoral response was analysed using either crude antigens (by ELISA and Western blotting) or several recombinant Leishmania antigens (Hsp70, Hsp83, LiP2a, LiP2b, H2A, H3 and KMP-11). From the analysis of all these parameters, we established the existence of three groups of animals: symptomatic or susceptible, oligosymptomatic, and resistant. Given the parallelism existing between the outcomes of Leishmania-infection in hamsters, dogs and humans, we believe that our data illustrate that the hamster is an excellent experimental model to study visceral leishmaniasis and for the design of vaccine development.

[1]  G. Freeman,et al.  Cloning of Syrian Hamster (Mesocricetus auratus) Cytokine cDNAs and Analysis of Cytokine mRNA Expression in Experimental Visceral Leishmaniasis , 1998, Infection and Immunity.

[2]  F. Derouin,et al.  Influence of the host and parasite strain in a mouse model of visceral Leishmania infantum infection. , 1998, FEMS immunology and medical microbiology.

[3]  R. Killick-Kendrick,et al.  Cellular and humoral immune responses in dogs experimentally and naturally infected with Leishmania infantum , 1994, Infection and immunity.

[4]  F. Martínez-Moreno,et al.  Humoral and cell-mediated immunity in natural and experimental canine leishmaniasis. , 1995, Veterinary immunology and immunopathology.

[5]  M. Roque-Barreira,et al.  Immune complex glomerulonephritis in experimental kala‐azar , 1987, Parasite immunology.

[6]  M. Roque-Barreira,et al.  Immune complex glomerulonephritis in experimental kala‐azar II: Detection and characterization of parasite antigens and antibodies eluted from kidneys of Leishmania donovani‐infected hamsters , 1992, Clinical and experimental immunology.

[7]  Y. Belkaid,et al.  The outcome of the parasitic process initiated by Leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the Lsh and MHC loci. , 1996, Journal of immunology.

[8]  H. Murray,et al.  Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis. , 1995, The Journal of clinical investigation.

[9]  A. C. Ghose,et al.  Therapeutic and prophylactic uses of protein A in the control of Leishmania donovani infection in experimental animals. , 1999, Immunology letters.

[10]  V. Rodrigues,et al.  Transforming Growth Factor β and Immunosuppression in Experimental Visceral Leishmaniasis , 1998, Infection and Immunity.

[11]  P. Bories,et al.  Lack of a nitric-oxide response during the course of Leishmania infantum infection in the golden hamster (Mesocricetus auratus), with or without treatment with liposomal amphotericin B. , 1998, Annals of tropical medicine and parasitology.

[12]  R. Vasconcellos,et al.  Suppressor activity in Leishmania donovani-infected hamster serum: reversion by delipidated bovine serum albumin and role in cell cycle events. , 1996, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[13]  R. Locksley,et al.  The regulation of immunity to Leishmania major. , 1995, Annual review of immunology.

[14]  C. Jaffe,et al.  An experimental model for canine visceral leishmaniasis , 1991, Parasite immunology.

[15]  R. López-Vélez,et al.  Leishmania and human immunodeficiency virus coinfection: the first 10 years , 1997, Clinical microbiology reviews.

[16]  J. Keithly.  Infectivity of Leishmania donovani amastigotes and promastigotes for golden hamsters. , 1976, The Journal of protozoology.

[17]  Y. Schlein,et al.  The effect of post-bloodmeal nutrition of Phlebotomus papatasi on the transmission of Leishmania major. , 1986, The American journal of tropical medicine and hygiene.

[18]  L. Moldawer,et al.  Role and effect of TNF-alpha in experimental visceral leishmaniasis. , 1994, Journal of immunology.

[19]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[20]  J. M. Alunda,et al.  Antibody response in dogs experimentally infected with Leishmania infantum: infection course antigen markers. , 1996, Experimental parasitology.

[21]  C. Jaffe,et al.  Analysis of immune responses in dogs with canine visceral leishmaniasis before, and after, drug treatment. , 1999, Veterinary immunology and immunopathology.

[22]  J. Farrell,et al.  Comparison of T-cell responses in self-limiting versus progressive visceral Leishmania donovani infections in golden hamsters , 1989, Infection and immunity.

[23]  P. Kaye,et al.  Neutralization of IL‐12 demonstrates the existence of discrete organ‐specific phases in the control of Leishmania donovani , 1998, European journal of immunology.

[24]  R. Pearson,et al.  Clinical spectrum of Leishmaniasis. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  L. A. Stauber,et al.  The origin and significance of the distribution of parasites in visceral leishmaniasis. , 1966, Transactions of the New York Academy of Sciences.

[26]  F. Liew,et al.  Immunology of leishmaniasis. , 1993, Advances in parasitology.

[27]  J. van Lunzen,et al.  Visceral leishmaniasis emerging as an important opportunistic infection in HIV-infected persons living in areas nonendemic for Leishmania donovani. , 1996, Archives of pathology & laboratory medicine.

[28]  J. M. Requena,et al.  Analysis of the humoral immune response against total and recombinant antigens of Leishmania infantum: correlation with disease progression in canine experimental leishmaniasis. , 1999, Veterinary immunology and immunopathology.

[29]  F. Afrin,et al.  Adjuvanticity and protective immunity elicited by Leishmania donovani antigens encapsulated in positively charged liposomes , 1997, Infection and immunity.

[30]  J. Quaranta,et al.  Visceral leishmaniosis in HIV‐positive patients: primary infection, reactivation and latent infection. Impact of the CD4+ T‐lymphocyte counts , 1998, AIDS.

[31]  M. Riyad,et al.  Immune response against Leishmania antigens in dogs naturally and experimentally infected with Leishmania infantum. , 1999, Veterinary parasitology.