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Babesia bovis: lipids from virulent S2P and attenuated R1A strains trigger differential signalling and inflammatory responses in bovine macrophages

Published online by Cambridge University Press:  03 January 2013

G. GIMENEZ*
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
M. L. BELAUNZARÁN
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
C. V. PONCINI
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
F. C. BLANCO
Affiliation:
Instituto de Biotecnología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, INTA-Castelar, Nicolas Repetto y de los Reseros s/n, 1686 Hurlingham, Buenos Aires, Argentina
I. ECHAIDE
Affiliation:
Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Agropecuaria Rafaela, Ruta 34 km 227, 2300 Santa Fe, Argentina
P. I. ZAMORANO
Affiliation:
Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, INTA-Castelar, Nicolas Repetto y de los Reseros s/n, 1686 Hurlingham, Buenos Aires, Argentina
E. M. LAMMEL
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
S. M. GONZÁLEZ CAPPA
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
E. L. D. ISOLA
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
*
*Corresponding author: Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina. Tel: +54 11 5950 9500 ext. 2191. Fax: +54 11 5950 9577. E-mail: paradife@fmed.uba.ar

Summary

The intra-erythrocytic protozoan Babesia bovis is an economically important pathogen that causes an acute and often fatal infection in adult cattle. Babesiosis limitation depends on the early activation of macrophages, essential cells of the host innate immunity, which can generate an inflammatory response mediated by cytokines and nitric oxide (NO). Herein, we demonstrate in bovine macrophages that lipids from B. bovis attenuated R1A strain (LA) produced a stronger NO release, an early TNFα mRNA induction and 2-fold higher IL-12p35 mRNA levels compared to the lipids of virulent S2P strain (LV). Neither LA nor LV induced anti-inflammatory IL-10. Regarding signalling pathways, we here report that LA induced a significant phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) whereas LV only induced a reduced activation of ERK1/2. Besides, NF-κB was activated by LA and LV, but LA produced an early degradation of the inhibitor IκB. Interestingly, LV and the majority of its lipid fractions, exerted a significant inhibition of concanavalin A-induced peripheral blood mononuclear cell proliferation with respect to LA and its corresponding lipid fractions. In addition, we determined that animals infected with R1A developed a higher increase in IgM anti-phosphatidylcholine than those inoculated with S2P. Collectively, S2P lipids generated a decreased inflammatory response contributing to the evasion of innate immunity. Moreover, since R1A lipids induced a pro-inflammatory profile, we propose these molecules as good candidates for immunoprophylactic strategies against babesiosis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2013

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References

REFERENCES

Anziani, O. S., Guglielmone, A. A., Abdala, A. A., Aguirre, D. H. and Mangold, A. J. (1993). Protección conferida por Babesia bovis vacunal en novillos Holando Argentino. Revista Medicina Veterinaria 74, 4749.Google Scholar
Baravalle, M. E., Thompson, C., Valentini, B., Ferreira, M., Torioni de Echaide, S., Florin-Christensen, M. and Echaide, I. (2012). Babesia bovis biological clones and the inter-strain allelic diversity of the Bv80 gene support subpopulation selection as a mechanism involved in the attenuation of two virulent isolates. Veterinary Parasitology http://dx.doi.org/10·1016/j.vetpar.2012·06·037.CrossRefGoogle ScholarPubMed
Baron, C. B., Cunningham, M., Strauss, J. F. 3rd and Coburn, R. F. (1984). Pharmacomechanical coupling in smooth muscle may involve phosphatidylinositol metabolism. Proceedings of the National Academy of Sciences, USA 81, 68996903.CrossRefGoogle ScholarPubMed
Blanco, F. C., Schierloh, P., Bianco, M. V., Caimi, K., Meikle, V., Alito, A. E., Cataldi, A. A., Sasiain M del, C. and Bigi, F. (2009). Study of the immunological profile towards Mycobacterium bovis antigens in naturally infected cattle. Microbiology and Immunology 53, 460467. doi:10.1111/j.1348-0421.2009.00141.x.CrossRefGoogle ScholarPubMed
Bligh, E. G. and Dyer, W. J. (1959). A rapid method of total lipid extraction and purification. Canadian Journal of Biochemical Physiology 37, 911917.CrossRefGoogle ScholarPubMed
Bock, R., Jackson, L., de Vos, A. and Jorgensen, W. (2004). Babesiosis of cattle. Parasitology 129, S247269. doi:10.1017/S0031182004005190.CrossRefGoogle ScholarPubMed
Brown, W. C., Norimine, J., Knowles, D. P. and Goff, W. L. (2006). Immune control of Babesia bovis infection. Veterinary Parasitology 138, 7587. doi:10.1016/j.vetpar.2006.01.041.CrossRefGoogle ScholarPubMed
Brown, W. C. and Palmer, G. H. (1999). Designing blood-stage vaccines against Babesia bovis and B. bigemina. Parasitology Today 15, 275281.CrossRefGoogle ScholarPubMed
Coussens, P. M., Verman, N., Coussens, M. A., Elftman, M. D. and McNulty, A. M. (2004). Cytokine gene expression in peripheral blood mononuclear cells and tissues of cattle infected with Mycobacterium avium subsp. paratuberculosis: evidence for an inherent proinflammatory gene expression pattern. Infection and Immunity 72, 14091422.CrossRefGoogle ScholarPubMed
Chen, C-C., Sun, Y-T., Chen, J-J. and Chiu, K-T. (2000). TNF-α-induced cyclooxigenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-γ2, protein kinase C-a, tyrosine kinase, NF-kB-inducing kinase, and I-kB kinase 1/2 pathway. Journal of Immunology 165, 27192728.CrossRefGoogle Scholar
Eligini, S., Brambilla, M., Banfi, C., Camera, M., Sironi, L., Barbieri, S. S., Auwerx, J., Tremoli, E. and Colli, S. (2002). Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-kB/I-kB- and ERK2-dependent mechanisms. Cardiovascular Research 55, 406415.CrossRefGoogle Scholar
Fell, A. H. and Smith, N. C. (1998). Immunity to asexual blood stages of Plasmodium: is resistance to acute malaria adaptive or innate? Parasitology Today 14, 364369.CrossRefGoogle ScholarPubMed
Feng, G. J., Goodridge, H. S., Harnett, M. M., Wei, X. Q., Nikolaev, A. V., Higson, A. P. and Liew, F. Y. (1999). Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. Journal of Immunology 163, 64036412.CrossRefGoogle ScholarPubMed
Florin-Christensen, J., Suarez, C. E., Florin-Christensen, M., Hines, S. A., McElwain, T. F. and Palmer, G. H. (2000). Phosphatidylcholine formation is the predominant lipid biosynthetic event in the hemoparasite Babesia bovis. Molecular and Biochemical Parasitology 106, 147156.CrossRefGoogle ScholarPubMed
Gimenez, G., Florin-Christensen, M., Belaunzarán, M. L., Isola, E. L., Suarez, C. E. and Florin-Christensen, J. (2007). Evidence for a relationship between bovine erythrocyte lipid membrane peculiarities and immune pressure from ruminal ciliates. Veterinary Immunology and Immunopathology 119, 171179. doi:10.1016/j.vetimm.2007.05.012.CrossRefGoogle ScholarPubMed
Gimenez, G., Magalhaes, K. G., Belaunzarán, M. L., Poncini, C. V., Lammel, E. M., González Cappa, S. M., Bozza, P. T. and Isola, E. L. (2010). Lipids from attenuated and virulent Babesia bovis strains induce differential TLR2-mediated macrophage activation. Molecular Immunology 47, 747755. doi:10.1016/j.molimm.2009.10.014.CrossRefGoogle ScholarPubMed
Goodger, B. V., Commins, M. A., Waltisbuhl, D. J., Wright, I. G. and Rode-Bramanis, K. (1990). Babesia bovis: immunity induced by vaccination with a lipid enriched fraction. International Journal for Parasitology 20, 685687.CrossRefGoogle ScholarPubMed
Hayden, M. S. and Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell 132, 344362. doi:10.1016/j.cell.2008.01.020.CrossRefGoogle ScholarPubMed
Hisaeda, H., Yasutomo, K. and Himeno, K. (2005). Malaria: immune evasion by parasites. The International Journal of Biochemistry & Cell Biology 37, 700706.CrossRefGoogle ScholarPubMed
Johnson, W. C., Cluff, C. W., Goff, W. L. and Wyatt, C. R. (1996). Reactive oxygen and nitrogen intermediates and products from polyamine degradation are Babesiacidal in vitro. Annals of the New York Academy of Sciences 791, 136147.CrossRefGoogle ScholarPubMed
Kaplan, G., Gandhi, R. R., Weinstein, D. E., Levis, W. R., Patarroyo, M. E., Brennan, P. J. and Cohn, Z. A. (1987). Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. Journal of Immunology 138, 30283034.CrossRefGoogle ScholarPubMed
Krause, P. J., Daily, J., Telford, S. R., Vannier, E., Lantos, P. and Spielman, A. (2007). Shared features in the pathobiology of babesiosis and malaria. Trends in Parasitology 23, 605610.CrossRefGoogle ScholarPubMed
Levy, M. G. and Ristic, M. (1980). Babesia bovis: continuous cultivation in a microaerophilous stationary phase culture. Science 207, 12181220.CrossRefGoogle Scholar
Mangold, A. J., Aguirre, D. H., Cafrune, M. M., de Echaide, S. T. and Guglielmone, A. A. (1993). Evaluation of the infectivity of a vaccinal and a pathogenic Babesia bovis strain from Argentina to Boophilus microplus. Veterinary Parasitology 51, 143148.CrossRefGoogle Scholar
Montealegre, F., Levy, M. G., Ristic, M. and James, M. A. (1985). Growth inhibition of Babesia bovis in culture by secretions from bovine mononuclear phagocytes. Infection and Immunity 50, 523526.CrossRefGoogle ScholarPubMed
Pahlevan, A. A., Wright, D. J., Andrews, C., George, K. M., Small, P. L. and Foxwell, B. M. (1999). The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function. Journal of Immunology 163, 39283935.CrossRefGoogle ScholarPubMed
Pfaffl, M. W., Horgan, G. W. and Dempfle, L. (2002). Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 30, e36.CrossRefGoogle Scholar
Quesniaux, V. J., Nicolle, D. M., Torres, D., Kremer, L., Guerardel, Y., Nigou, J., Puzo, G., Erard, F. and Ryffel, B. (2004). Toll-like receptor 2 (TLR2)-dependent-positive and TLR2-independent-negative regulation of proinflammatory cytokines by mycobacterial lipomannans. Journal of Immunology 172, 44254434.CrossRefGoogle ScholarPubMed
Reiling, N., Blumenthal, A., Flad, H. D., Ernst, M. and Ehlers, S. (2001). Mycobacteria-induced TNF-alpha and IL-10 formation by human macrophages is differentially regulated at the level of mitogen-activated protein kinase activity. Journal of Immunology 167, 33393345.CrossRefGoogle ScholarPubMed
Riedel, D. D. and Kaufmann, S. H. (2000). Differential tolerance induction by lipoarabinomannan and lipopolysaccharide in human macrophages. Microbes and Infecion 2, 463471.CrossRefGoogle ScholarPubMed
Roach, S. K. and Schorey, J. S. (2002). Differential regulation of the mitogen-activated protein kinases by pathogenic and nonpathogenic mycobacteria. Infection and Immunity 70, 30403052. doi:10.1128/IAI.70.6.3040-3052.2002.CrossRefGoogle ScholarPubMed
Roach, T. I., Barton, C. H., Chatterjee, D. and Blackwell, J. M. (1993). Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. Journal of Immunology 150, 18861896.CrossRefGoogle ScholarPubMed
Ruckdeschel, K., Machold, J., Roggenkamp, A., Schubert, S., Pierre, J., Zumbihl, R., Liautard, J. P., Heesemann, J. and Rouot, B. (1997). Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production. Journal of Biological Chemistry 272, 1592015927.CrossRefGoogle Scholar
Sabat, R., Grütz, G., Warszawska, K., Kirsch, S., Witte, E., Wolk, K. and Geginat, J. (2010). Biology of interleukin-10. Cytokine Growth Factor Reviews 21, 331344.CrossRefGoogle ScholarPubMed
Schofield, L. and Hackett, F. (1993). Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. Journal of Experimental Medicine 177, 145153.CrossRefGoogle ScholarPubMed
Shoda, L. K., Palmer, G. H., Florin-Christensen, J., Florin-Christensen, M., Godson, D. L. and Brown, W. C. (2000). Babesia bovis-stimulated macrophages express interleukin-1beta, interleukin-12, tumor necrosis factor alpha, and nitric oxide and inhibit parasite replication in vitro. Infection and Immunity 68, 51395145.CrossRefGoogle ScholarPubMed
Souza, C. D., Evanson, O. A. and Weiss, D. J. (2007). Role of the mitogen-activated protein kinase pathway in the differential response of bovine monocytes to Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium. Microbes and Infection 9, 15451552.CrossRefGoogle ScholarPubMed
Stich, R. W., Shoda, L. K., Dreewes, M., Adler, B., Jungi, T. W. and Brown, W. C. (1998). Stimulation of nitric oxide production in macrophages by Babesia bovis. Infection and Immunity 66, 41304136.CrossRefGoogle ScholarPubMed
Surewicz, K., Aung, H., Kanost, R. A., Jones, L., Hejal, R. and Toossi, Z. (2004). The differential interaction of p38 MAP kinase and tumor necrosis factor-alpha in human alveolar macrophages and monocytes induced by Mycobacterium tuberculois. Cellular Immunology 228, 3441. doi:10.1016/j.cellimm.2004.03.007.CrossRefGoogle ScholarPubMed
Trinchieri, G. (1995). Interleukin 12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annual Review of Immunology 13, 251276. doi:10.1146/annurev.iy.13.040195.001343.CrossRefGoogle ScholarPubMed
Verma, I. M., Stevenson, J. K., Schwarz, E. M., Van Antwerp, D. and Miyamoto, S. (1995). Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes and Development 9, 27232735. doi:10.1101/gad.9.22.2723.CrossRefGoogle ScholarPubMed
Wright, I. G., Goodger, B. V. and Clark, I. A. (1988). Immunopathophysiology of Babesia bovis and Plasmodium falciparum infections. Parasitology Today 4, 214218.CrossRefGoogle ScholarPubMed
Wykes, M., Keighley, C., Pinzon-Charry, A. and Good, M. F. (2007). Dendritic cell biology during malaria. Cellular Microbiology 9, 300305.CrossRefGoogle ScholarPubMed
Yadav, M., Roach, S. K. and Schorey, J. S. (2004). Increased mitogen-activated protein kinase activity and TNF-alpha production associated with Mycobacterium smegmatis- but not Mycobacterium avium-infected macrophages requires prolonged stimulation of the calmodulin/calmodulin kinase and cyclic AMP/protein kinase A pathways. Journal of Immunology 172, 55885597.CrossRefGoogle Scholar