Hostname: page-component-7479d7b7d-68ccn Total loading time: 0 Render date: 2024-07-10T19:27:37.691Z Has data issue: false hasContentIssue false
  • English
  • Français

Cytokine expression in dogs with natural Leishmania infantum infection

Published online by Cambridge University Press:  02 June 2009

M. A. PANARO ,
O. BRANDONISIO ,
A. CIANCIULLI ,
P. CAVALLO ,
V. LACASELLA ,
P. PARADIES ,
G. TESTINI ,
D. DE CAPRARIIS ,
V. MITOLO  and
D. OTRANTO
M. A. PANARO
Affiliation:
Department of Human Anatomy and Histology, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
O. BRANDONISIO
Affiliation:
Department of Internal Medicine, Immunology and Infectious Diseases, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
A. CIANCIULLI
Affiliation:
Department of Human Anatomy and Histology, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
P. CAVALLO
Affiliation:
Department of Human Anatomy and Histology, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
V. LACASELLA
Affiliation:
Department of Internal Medicine, Immunology and Infectious Diseases, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
P. PARADIES
Affiliation:
Department of Veterinary Public Health, Faculty of Veterinary Medicine, University of Bari, Strada Provinciale per Casamassima Km. 3, 70010 Valenzano, Bari, Italy
G. TESTINI
Affiliation:
Department of Veterinary Public Health, Faculty of Veterinary Medicine, University of Bari, Strada Provinciale per Casamassima Km. 3, 70010 Valenzano, Bari, Italy
D. DE CAPRARIIS
Affiliation:
Department of Veterinary Public Health, Faculty of Veterinary Medicine, University of Bari, Strada Provinciale per Casamassima Km. 3, 70010 Valenzano, Bari, Italy
V. MITOLO
Affiliation:
Department of Human Anatomy and Histology, Faculty of Medicine, University of Bari, Piazza G. Cesare, 70100 Bari, Italy
D. OTRANTO*
Affiliation:
Department of Veterinary Public Health, Faculty of Veterinary Medicine, University of Bari, Strada Provinciale per Casamassima Km. 3, 70010 Valenzano, Bari, Italy
*
*Corresponding author: Department of Veterinary Public Health, Faculty of Veterinary Medicine, University of Bari, Strada Provinciale per Casamassima Km. 3, 70010 Valenzano, Bari, Italy. Tel/fax: +39 080 4679839. E-mail: d.otranto@veterinaria.uniba.it
Get access Rights & Permissions [Opens in a new window]

Summary

The aim of this study was to evaluate cytokine expression in 22 Leishmania infantum naturally infected dogs, in order to correlate this parameter with the clinical status of infected animals. After 4 and 8 months from the first diagnosis of Leishmania infection, clinical and laboratory examination of dogs was performed and peripheral blood mononuclear cells (PBMC) were isolated. The cytokine profile was analysed in terms of IFN-gamma, IL-4, IL-10 and TNF-alpha mRNA expression in cultured PBMC by a semi-quantitative reverse transcriptase-PCR. Thirteen out of 22 Leishmania-infected dogs remained asymptomatic in the follow-up, while 9 showed clinical signs of leishmaniasis. IL-4, IL-10, TNF-alpha and IFN-gamma mRNA levels were not significantly different in asymptomatic compared to symptomatic animals 4 months from the diagnosis of Leishmania infection, but were significantly higher in symptomatic versus asymptomatic dogs after 8 months from diagnosis. In addition, IL-4, IL-10 and TNF-alpha mRNA levels significantly increased only in symptomatic dogs at 8 months, in comparison to the levels found at 4 months. These results show a mixed Th1 and Th2 cytokine response in Leishmania-infected dogs, with higher cytokine expression in dogs with manifest clinical disease, during the second follow-up after 8 months from the first diagnosis of infection.

Keywords

Leishmaniacanine leishmaniasisIFN-gammaIL-10IL-4TNF-alpha
Type
Research Article
Information
Parasitology , Volume 136 , Issue 8 , July 2009 , pp. 823 - 831
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alvar, J., Aparicio, P., Aseffa, A., Den Boer, M., Cañavate, C., Dedet, J. P., Gradoni, L., Ter Horst, R., López-Vélez, R. and Moreno, J. (2008). The relationship between leishmaniasis and AIDS: the second 10 years. Clinical Microbiology Reviews 21, 334–359.Google Scholar
Alvar, J., Yactayo, S. and Bern, C. (2006) Leishmaniasis and poverty. Trends in Parasitology 22, 552–557.CrossRefGoogle ScholarPubMed
Alves, C. F., de Amorim, I. F., Moura, E. P., Ribeiro, R. R., Alves, C. F., Michalick, M. S., Kalapothakis, E., Bruna-Romero, O., Tafuri, W. L., Teixeira, M. M. and Melo, M. N. (2008). Expression of IFN-gamma, TNF-alpha, IL-10 and TGF-beta in lymph nodes associates with parasite load and clinical form of disease in dogs naturally infected with Leishmania (Leishmania) chagasi. Veterinary Immunology and Immunopathology Nov 17 [Epub ahead of print].Google ScholarPubMed
Anderson, C. F., Lira, R., Kamhawi, S., Belkaid, Y., Wynn, T. A. and Sacks, D. (2008). IL-10 and TGF-beta control the establishment of persistent and transmissible infections produced by Leishmania tropica in C57BL/6 mice. The Journal of Immunology 180, 4090–4097.CrossRefGoogle ScholarPubMed
Baneth, G., Koutinas, A. F., Solano-Gallego, L., Bourdeau, P. and Ferrer, L. (2008). Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part one. Trends in Parasitology 24, 324–330.CrossRefGoogle Scholar
Barbiéri, C. L. (2006). Immunology of canine leishmaniasis. Parasite Immunology 28, 329–337.CrossRefGoogle ScholarPubMed
Blackwell, J. M. (1999). Tumour necrosis factor alpha and mucocutaneous leishmaniasis. Parasitology Today 15, 73–75.Google Scholar
Bogdan, C., Röllinghoff, M. and Diefenbach, A. (2000). Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology 12, 64–76.CrossRefGoogle ScholarPubMed
Brachelente, C., Müller, N., Doherr, M. G., Sattler, U. and Welle, M. (2005). Cutaneous leishmaniasis in naturally infected dogs is associated with a T helper-2-biased immune response. Veterinary Pathology 42, 166–175.Google Scholar
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Brandonisio, O., Carelli, G., Ceci, L., Consenti, B., Fasanella, A. and Puccini, V. (1992). Canine leishmaniasis in the Gargano promontory (Apulia, South Italy). European Journal of Epidemiology 8, 273–276.Google Scholar
Brandonisio, O., Panaro, M. A., Fumarola, I., Sisto, M., Leogrande, D., Acquafredda, A., Spinelli, R. and Mitolo, V. (2002). Macrophage chemotactic protein-1 and macrophage inflammatory protein-1 alpha induce nitric oxide release and enhance parasite killing in Leishmania infantum-infected human macrophages. Clinical and Experimental Medicine 2, 125–129.Google Scholar
Campos-Neto, A. (2005). What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery? Brazilian Journal of Medical and Biological Research 38, 979–984.Google Scholar
Carrillo, E., Ahmed, S., Goldsmith-Pestana, K., Nieto, J., Osorio, Y., Travi, B., Moreno, J. and McMahon-Pratt, D. (2007). Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis. Vaccine 25, 1534–1543.CrossRefGoogle ScholarPubMed
Carrillo, E., Crusat, M., Nieto, J., Chicharro, C., Thomas Mdel, C., Martínez, E., Valladares, B., Cañavate, C., Requena, J. M., López, M. C., Alvar, J. and Moreno, J. (2008). Immunogenicity of HSP-70, KMP-11 and PFR-2 leishmanial antigens in the experimental model of canine visceral leishmaniasis. Vaccine 26, 1902–1911.Google Scholar
Carrillo, E. and Moreno, J. (2008). Cytokine profiles in canine visceral leishmaniasis. Veterinary Immunology and Immunopathology Oct 17 [Epub ahead of print].Google Scholar
Corrêa, A. P., Dossi, A. C., de Oliveira Vasconcelos, R., Munari, D. P. and de Lima, V. M. (2007). Evaluation of transformation growth factor beta1, interleukin-10, and interferon-gamma in male symptomatic and asymptomatic dogs naturally infected by Leishmania (Leishmania) chagasi. Veterinary Parasitology 143, 267–274.CrossRefGoogle ScholarPubMed
Chamizo, C., Moreno, J. and Alvar, J. (2005). Semi-quantitative analysis of cytokine expression in asymptomatic canine leishmaniasis. Veterinary Immunology and Immunopathology 103, 67–75.CrossRefGoogle ScholarPubMed
Chappuis, F., Sundar, S., Hailu, A., Ghalib, H., Rijal, S., Peeling, R. W., Alvar, J. and Boelaert, M. (2007). Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nature Reviews Microbiology 5, 873–882.Google Scholar
Dantas-Torres, F. (2007). The role of dogs as reservoirs of Leishmania parasites, with emphasis on Leishmania (Leishmania) infantum and Leishmania (Viannia) braziliensis. Veterinary Parasitology 149, 139–146.Google Scholar
Dujardin, J. C., Campino, L., Cañavate, C., Dedet, J. P., Gradoni, L., Soteriadou, K., Mazeris, A., Ozbel, Y. and Boelaert, M. (2008). Spread of vector-borne diseases and neglect of Leishmaniasis, Europe. Emerging Infectious Diseases 14, 1013–1018.Google Scholar
Gröne, A., Weckmann, M. T., Capen, C. C. and Rosol, T. J. (1996). Canine glyceraldehyde-3-phosphate dehydrogenase complementary DNA: polymerase chain reaction amplification, cloning, partial sequence analysis, and use as loading control in ribonuclease protection assays. American Journal of Veterinary Research 57, 254–257.CrossRefGoogle ScholarPubMed
Khalil, E. A., Ayed, N. B., Musa, A. M., Ibrahim, M. E., Mukhtar, M. M., Zijlstra, E. E., Elhassan, I. M., Smith, P. G., Kieny, P. M., Ghalib, H. W., Zicker, F., Modabber, F. and Elhassan, A. M. (2005). Dichotomy of protective cellular immune responses to human visceral leishmaniasis. Clinical & Experimental Immunology 140, 349–353.CrossRefGoogle ScholarPubMed
Lage, R. S., Oliveira, G. C., Busek, S. U., Guerra, L. L., Giunchetti, R. C., Corrêa-Oliveira, R. and Reis, A. B. (2007). Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi. Veterinary Immunology and Immunopathology 115, 135–145.Google Scholar
Lemesre, J. L., Holzmuller, P., Gonçalves, R. B., Bourdoiseau, G., Hugnet, C., Cavaleyra, M. and Papierok, G. (2007). Long-lasting protection against canine visceral leishmaniasis using the LiESAp-MDP vaccine in endemic areas of France: double-blind randomised efficacy field trial. Vaccine 25, 4223–4234.Google Scholar
Louassini, M., Adroher, F. J., Foulquie, M. R. and Benitez, R. (1998). Investigations on the in vitro metacyclogenesis of a visceral and a cutaneous human strain of Leishmania infantum. Acta Tropica 70, 355–368.CrossRefGoogle Scholar
Manna, L., Reale, S., Viola, E., Vitale, F., Manzillo, V. F., Michele, P. L., Caracappa, S. and Gravino, A. E. (2006). Leishmania DNA load and cytokine expression levels in asymptomatic naturally infected dogs. Veterinary Parasitology 142, 271–280.Google Scholar
Mansueto, P., Vitale, G., Di Lorenzo, G., Rini, G. B., Mansueto, S. and Cillari, E. (2007). Immunopathology of leishmaniasis: an update. International Journal of Immunopathology and Pharmacology 20, 435–445.Google Scholar
Maroli, M., Rossi, L., Baldelli, R., Capelli, G., Ferroglio, E., Genchi, C., Gramiccia, M., Mortarino, M., Pietrobelli, M. and Gradoni, L. (2008). The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing studies on the canine reservoir and phlebotomine vectors. Tropical Medicine & International Health 13, 256–264.Google Scholar
Michalsky, E. M., Rocha, M. F., da Rocha Lima, A. C., França-Silva, J. C., Pires, M. Q., Oliveira, F. S., Pacheco, R. S., dos Santos, S. L., Barata, R. A., Romanha, A. J., Fortes-Dias, C. L. and Dias, E. S. (2007). Infectivity of seropositive dogs, showing different clinical forms of leishmaniasis, to Lutzomyia longipalpis phlebotomine sand flies. Veterinary Parasitology 147, 67–76.Google Scholar
Miró, G., Cardoso, L., Pennisi, M. G., Oliva, G. and Baneth, G. (2008). Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part two. Trends in Parasitology 24, 371–377.Google Scholar
Nylén, S. and Sacks, D. (2007). Interleukin-10 and the pathogenesis of human visceral leishmaniasis. Trends in Immunology 28, 378–384.Google Scholar
Oliva, G., Scalone, A., Foglia Manzillo, V., Gramiccia, M., Pagano, A., Di Muccio, T. and Gradoni, L. (2006). Incidence and time course of Leishmania infantum infections examined by parasitological, serologic, and nested-PCR techniques in a cohort of naive dogs exposed to three consecutive transmission seasons. Journal of Clinical Microbiology 44, 1318–1322.Google Scholar
Olivier, M. and Gregory, D. J. (2008). Interactions between Leishmania and the host macrophage. In Leishmania: after The Genome (ed. Myler, P. J. and Fasel, N.), pp. 239–262. Caister Academic Press, Linton, UK.Google Scholar
Otranto, D., Paradies, P., de Caprariis, D., Stanneck, D., Testini, G., Grimm, F., Deplazes, P. and Capelli, G. (2009). Toward diagnosing Leishmania infantum infection in asymptomatic dogs in endemic area. Clinical and Vaccine Immunololgy 16, 337–343.Google Scholar
Otranto, D., Paradies, P., Lia, R. P., Latrofa, M. S., Testini, G., Cantacessi, C., Mencke, N., Galli, G., Capelli, G. and Stanneck, D. (2007). Efficacy of a combination of 10% imidacloprid/50% permethrin for the prevention of leishmaniasis in kennelled dogs in an endemic area. Veterinary Parasitology 144, 270–278.CrossRefGoogle Scholar
Palatnik-de-Sousa, C. B. (2008). Vaccines for leishmaniasis in the fore coming 25 years. Vaccine 26, 1709–1724.Google Scholar
Panaro, M. A., Acquafredda, A., Lisi, S., Lofrumento, D. D., Mitolo, V., Sisto, M., Fasanella, A., Trotta, T., Bertani, F., Consenti, B. and Brandonisio, O. (2001). Nitric oxide production by macrophages of dogs vaccinated with killed Leishmania infantum promastigotes. Comparative Immunology, Microbiology & Infectious Diseases 24, 187–195.Google Scholar
Panaro, M. A., Brandonisio, O., de Caprariis, D., Cavallo, P., Cianciulli, A., Mitolo, V. and Otranto, D. (2008). Canine leishmaniasis in Southern Italy: a role for nitric oxide released from activated macrophages in asymptomatic infection? Parasites & Vectors 1, 10. doi:10.1186/1756-3305-1-10.Google Scholar
Paradies, P., Capelli, G., Cafarchia, C., de Caprariis, D., Sasanelli, M. and Otranto, D. (2006). Incidences of canine leishmaniasis in an endemic area of southern Italy. Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health 53, 295–298.CrossRefGoogle Scholar
Pfaff, A. W., Abou-Bacar, A., Letscher-Bru, V., Villard, O., Senegas, A., Mousli, M. and Candolfi, E. (2007). Cellular and molecular physiopathology of congenital toxoplasmosis: the dual role of IFN-gamma. Parasitology 134, 1895–1902.Google Scholar
Pinelli, E., Gonzalo, R. M., Boog, C. J., Rutten, V. P., Gebhard, D., del Real, G. and Ruitenberg, E. J. (1995). Leishmania infantum-specific T cell lines derived from asymptomatic dogs that lyse infected macrophages in a major histocompatibility complex-restricted manner. European Journal of Immunology 25, 1594–1600.Google Scholar
Pinelli, E., Killick-Kendrick, R., Wagenaar, J., Bernadina, W., del Real, G. and Ruitenberg, J. (1994). Cellular and humoral immune responses in dogs experimentally and naturally infected with Leishmania infantum. Infection and Immunity 62, 229–235.CrossRefGoogle ScholarPubMed
Poot, J., Spreeuwenberg, K., Sanderson, S. J., Schijns, V. E., Mottram, J. C., Coombs, G. H. and Vermeulen, A. N. (2006). Vaccination with a preparation based on recombinant cysteine peptidases and canine IL-12 does not protect dogs from infection with Leishmania infantum. Vaccine 24, 2460–2468.CrossRefGoogle Scholar
Quinnell, R. J., Courtenay, O., Shaw, M. A., Day, M. J., Garcez, L. M., Dye, C. and Kaye, P. M. (2001). Tissue cytokine responses in canine visceral leishmaniasis. Journal of Infectious Diseases 183, 1421–1424.Google Scholar
Sanchez-Robert, E., Altet, L., Alberola, J., Rodriguez-Cortés, A., Ojeda, A., López-Fuertes, L., Timon, M., Sanchez, A. and Francino, O. (2008). Longitudinal analysis of cytokine gene expression and parasite load in PBMC in Leishmania infantum experimentally infected dogs. Veterinary Immunology and Immunopathology 125, 168–175.Google Scholar
Santos-Gomes, G. M., Rosa, R., Leandro, C., Cortes, S., Romão, P. and Silveira, H. (2002). Cytokine expression during the outcome of canine experimental infection by Leishmania infantum. Veterinary Immunology and Immunopathology 88, 21–30.CrossRefGoogle ScholarPubMed
Schmelzer, C., Lorenz, G., Rimbach, G. and Döring, F. (2009). In vitro effects of the reduced form of coenzyme Q(10) on secretion levels of TNF-alpha and chemokines in response to LPS in the human monocytic cell line THP-1. Journal of Clinical Biochemistry and Nutrition 44, 62–66.Google Scholar
Schönian, G., Mauricio, I., Gramiccia, M., Cañavate, C., Boelaert, M. and Dujardin, J. C. (2008). Leishmaniases in the Mediterranean in the era of molecular epidemiology. Trends in Parasitology 24, 135–142.Google Scholar
Strauss-Ayali, D., Baneth, G. and Jaffe, C. L. (2007). Splenic immune responses during canine visceral leishmaniasis. Veterinary Research 38, 547–564.Google Scholar
Strauss-Ayali, D., Baneth, G., Shor, S., Okano, F. and Jaffe, C. L. (2005). Interleukin-12 augments a Th1-type immune response manifested as lymphocyte proliferation and interferon gamma production in Leishmania infantum-infected dogs. International Journal for Parasitology 35, 63–73.Google Scholar
Tacchini-Cottier, F. and Launois, P. (2008). Host responses to infections with Leishmania. In Leishmania: after The Genome (ed. Myler, P. J. and Fasel, N.), pp. 263–279. Caister Academic Press, Linton, UK.Google Scholar
Wilson, M. E., Jeronimo, S. M. B. and Pearson, R. D. (2005). Immunopathogenesis of infection with the visceralizing Leishmania species. Microbial Pathogenesis 38, 147–160.Google Scholar
Zafra, R., Jaber, J. R., Pérez-Ecija, R. A., Barragán, A., Martínez-Moreno, A. and Pérez, J. (2008). High iNOS expression in macrophages in canine leishmaniasis is associated with low intracellular parasite burden. Veterinary Immunology and Immunopathology 123, 353–359.CrossRefGoogle ScholarPubMed