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Parasite genetic diversity does not influence TNF-mediated effects on the virulence of primary rodent malaria infections

Published online by Cambridge University Press:  18 September 2006

G. H. LONG ,
B. H. K. CHAN ,
J. E. ALLEN ,
A. F. READ  and
A. L. GRAHAM
G. H. LONG
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
B. H. K. CHAN
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
J. E. ALLEN
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
A. F. READ
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
A. L. GRAHAM
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
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Abstract

The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) is associated with malaria virulence (disease severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled for, a greater day 7 TNF-α response was induced by infection with more virulent P.c.c. clones. Since many functions of TNF-α are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections induced significantly different plasma interferon gamma (IFN-γ), interleukin 6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-α is a key mediator of weight loss, independent of parasite load and across parasite genotypes.

Keywords

malariaPlasmodium chabauditumour necrosis factor-α (TNF-α)parasite genotypevirulenceimmunopathologydisease severitycachexia
Type
Research Article
Information
Parasitology , Volume 133 , Issue 6 , December 2006 , pp. 673 - 684
Copyright
2006 Cambridge University Press

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References

REFERENCES

Alles, H. K., Mendis, K. N. and Carter, R. ( 1998). Malaria mortality rates in South Asia and in Africa: implications for malaria control. Parasitology Today 14, 369–375.CrossRefGoogle Scholar
Anstey, N. M., Weinberg, J. B., Hassanali, M. Y., Mwaikambo, E. D., Manyenga, D., Misukonis, M. A., Arnelle, D. R., Hollis, D., McDonald, M. I. and Granger, D. L. ( 1996). Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. Journal of Experimental Medicine 184, 557–567.CrossRefGoogle Scholar
Artavanis-Tsakonas, K., Tongren, J. E. and Riley, E. M. ( 2003). The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clinical and Experimental Immunology 133, 145–152.CrossRefGoogle Scholar
Ashkenazi, A., Marsters, S. A., Capon, D. J., Chamow, S. M., Figari, I. S., Pennica, D., Goeddel, D. V., Palladino, M. A. and Smith, D. H. ( 1991). Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proceedings of the National Academy of Sciences, USA 88, 10535–10539.CrossRefGoogle Scholar
Bate, C. A. and Kwiatkowski, D. ( 1994). A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum. Infection and Immunity 62, 5261–5266.Google Scholar
Bate, C. A., Taverne, J., Bootsma, H. J., Mason, R. C., Skalko, N., Gregoriadis, G. and Playfair, J. H. ( 1992). Antibodies against phosphatidylinositol and inositol monophosphate specifically inhibit tumour necrosis factor induction by malaria exoantigens. Immunology 76, 35–41.Google Scholar
Bate, C. A., Taverne, J. and Playfair, J. H. ( 1988). Malarial parasites induce TNF production by macrophages. Immunology 64, 227–231.Google Scholar
Bate, C. A., Taverne, J. and Playfair, J. H. ( 1989). Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology 66, 600–605.Google Scholar
Chotivanich, K., Udomsangpetch, R., Simpson, J. A., Newton, P., Pukrittayakamee, S., Looareesuwan, S. and White, N. J. ( 2000). Parasite multiplication potential and the severity of falciparum malaria. Journal of Infectious Diseases 181, 1206–1209.CrossRefGoogle Scholar
Clark, I. A., Alleva, L. M., Mills, A. C. and Cowden, W. B. ( 2004). Pathogenesis of malaria and clinically similar conditions. Clinical Microbial Reviews 17, 509–539.CrossRefGoogle Scholar
Clark, I. A. and Chaudhri, G. ( 1988 a). The balance of useful and harmful effects of TNF, with special reference to malaria. Annales de l'Institut Pasteur, Immunology 139, 305–306.Google Scholar
Clark, I. A. and Chaudhri, G. ( 1988 b). Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. British Journal of Haematology 70, 99–103.Google Scholar
Clark, I. A., Cowden, W. B., Butcher, G. A. and Hunt, N. H. ( 1983). Free oxygen radicals in malaria. Lancet 1, 359–360.CrossRefGoogle Scholar
Crooks, L. ( 2004). Gametocyte investment in malaria. Ph.D. thesis, University of Edinburgh.
de Roode, J. C., Pansini, R., Cheesman, S. J., Helinski, M. E., Huijben, S., Wargo, A. R., Bell, A. S., Chan, B. H., Walliker, D. and Read, A. F. ( 2005). Virulence and competitive ability in genetically diverse malaria infections. Proceedings of the National Academy of Sciences, USA 102, 7624–7628.CrossRefGoogle Scholar
Dodoo, D., Omer, F. M., Todd, J., Akanmori, B. D., Koram, K. A. and Riley, E. M. ( 2002). Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria. Journal of Infectious Diseases 185, 971–979.CrossRefGoogle Scholar
Ferguson, H. M., Mackinnon, M. J., Chan, B. H. and Read, A. F. ( 2003). Mosquito mortality and the evolution of malaria virulence. Evolution; International Journal of Organic Evolution 57, 2792–2804.CrossRefGoogle Scholar
Gazzinelli, R. T., Wysocka, M., Hieny, S., Scharton-Kersten, T., Cheever, A., Kuhn, R., Muller, W., Trinchieri, G. and Sher, A. ( 1996). In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. Journal of Immunology 157, 798–805.Google Scholar
Grafen, A. and Hails, R. ( 2002). Modern Statistics for the Life Sciences. Oxford University Press, Oxford.
Graham, A. L., Lamb, T. J., Read, A. F. and Allen, J. E. ( 2005). Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency. Journal of Infectious Diseases 191, 410–421.CrossRefGoogle Scholar
Grau, G. E., Del Giudice, G. and Lambert, P. H. ( 1987). Host immune response and pathological expression in malaria: possible implications for malaria vaccines. Parasitology 94 (Suppl.), S123–S137.CrossRefGoogle Scholar
Grau, G. E., Taylor, T. E., Molyneux, M. E., Wirima, J. J., Vassalli, P., Hommel, M. and Lambert, P. H. ( 1989). Tumor necrosis factor and disease severity in children with falciparum malaria. New England Journal of Medicine 320, 1586–1591.CrossRefGoogle Scholar
Gravenor, M. B., McLean, A. R. and Kwiatkowski, D. ( 1995). The regulation of malaria parasitaemia: parameter estimates for a population model. Parasitology 110, 115–122.CrossRefGoogle Scholar
Griffiths, M. J., Ndungu, F., Baird, K. L., Muller, D. P., Marsh, K. and Newton, C. R. ( 2001). Oxidative stress and erythrocyte damage in Kenyan children with severe Plasmodium falciparum malaria. British Journal of Haematology 113, 486–491.CrossRefGoogle Scholar
Hirunpetcharat, C., Finkelman, F., Clark, I. A. and Good, M. F. ( 1999). Malaria parasite-specific Th1-like T cells simultaneously reduce parasitemia and promote disease. Parasite Immunology 21, 319–329.CrossRefGoogle Scholar
Hunter, C. A., Ellis-Neyes, L. A., Slifer, T., Kanaly, S., Grunig, G., Fort, M., Rennick, D. and Araujo, F. G. ( 1997). IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi. Journal of Immunology 158, 3311–3316.Google Scholar
Jacobs, P., Radzioch, D. and Stevenson, M. M. ( 1996). A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice. Infection and Immunity 64, 535–541.Google Scholar
Jacobs, R. L. ( 1964). Role of p-aminobenzoic acid in Plasmodium berghei infection in the mouse. Experimental Parasitology 15, 213–225.CrossRefGoogle Scholar
Kebaier, C., Louzir, H., Chenik, M., Ben Salah, A. and Dellagi, K. ( 2001). Heterogeneity of wild Leishmania major isolates in experimental murine pathogenicity and specific immune response. Infection and Immunity 69, 4906–4915.CrossRefGoogle Scholar
Kern, P., Hemmer, C. J., Gallati, H., Neifer, S., Kremsner, P., Dietrich, M. and Porzsolt, F. ( 1992). Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria. Journal of Infectious Diseases 166, 930–934.CrossRefGoogle Scholar
Kremsner, P. G., Neifer, S., Chaves, M. F., Rudolph, R. and Bienzle, U. ( 1992). Interferon-gamma induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine. European Journal of Immunology 22, 2873–2878.CrossRefGoogle Scholar
Kullberg, M. C., Ward, J. M., Gorelick, P. L., Caspar, P., Hieny, S., Cheever, A., Jankovic, D. and Sher, A. ( 1998). Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent mechanism. Infection and Immunity 66, 5157–5166.Google Scholar
Kwiatkowski, D. ( 1990). Tumour necrosis factor, fever and fatality in falciparum malaria. Immunology Letters 25, 213–216.CrossRefGoogle Scholar
Kwiatkowski, D., Hill, A. V., Sambou, I., Twumasi, P., Castracane, J., Manogue, K. R., Cerami, A., Brewster, D. R. and Greenwood, B. M. ( 1990). TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201–1204.CrossRefGoogle Scholar
Langhorne, J., Albano, F. R., Hensmann, M., Sanni, L., Cadman, E., Voisine, C. and Sponaas, A. M. ( 2004). Dendritic cells, pro-inflammatory responses, and antigen presentation in a rodent malaria infection. Immunology Reviews 201, 35–47.CrossRefGoogle Scholar
Langhorne, J., Cross, C., Seixas, E., Li, C. and von der Weid, T. ( 1998). A role for B cells in the development of T cell helper function in a malaria infection in mice. Proceedings of the National Academy of Sciences, USA 95, 1730–1734.CrossRefGoogle Scholar
Langhorne, J., Meding, S. J., Eichmann, K. and Gillard, S. S. ( 1989). The response of CD4+ T cells to Plasmodium chabaudi chabaudi. Immunology Reviews 112, 71–94.CrossRefGoogle Scholar
Li, C., Corraliza, I. and Langhorne, J. ( 1999). A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice. Infection and Immunity 67, 4435–4442.Google Scholar
Li, C. and Langhorne, J. ( 2000). Tumor necrosis factor alpha p55 receptor is important for development of memory responses to blood-stage malaria infection. Infection and Immunity 68, 5724–5730.CrossRefGoogle Scholar
Li, C., Sanni, L. A., Omer, F., Riley, E. and Langhorne, J. ( 2003). Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor beta antibodies. Infection and Immunity 71, 4850–4856.CrossRefGoogle Scholar
Li, C., Seixas, E. and Langhorne, J. ( 2001). Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite. Medical Microbiology and Immunology 189, 115–126.CrossRefGoogle Scholar
Mackinnon, M. J., Gaffney, D. J. and Read, A. F. ( 2002). Virulence in rodent malaria: host genotype by parasite genotype interactions. Infection Genetics and Evolution 1, 287–296.CrossRefGoogle Scholar
Mackinnon, M. J. and Read, A. F. ( 1999 a). Genetic relationships between parasite virulence and transmission in the rodent malaria Plasmodium chabaudi. Evolution; International Journal of Organic Evolution 53, 689–703.Google Scholar
Mackinnon, M. J. and Read, A. F ( 1999 b). Selection for high and low virulence in the malaria parasite Plasmodium chabaudi. Proceedings of the Royal Society, Biological Sciences 266, 741–748.Google Scholar
Mackinnon, M. J. and Read, A. F. ( 2004). Virulence in malaria: an evolutionary viewpoint. Philosophical Transactions of the Royal Society of London, B 359, 965–986.CrossRefGoogle Scholar
Molyneux, M. E., Engelmann, H., Taylor, T. E., Wirima, J. J., Aderka, D., Wallach, D. and Grau, G. E. ( 1993). Circulating plasma receptors for tumour necrosis factor in Malawian children with severe falciparum malaria. Cytokine 5, 604–609.CrossRefGoogle Scholar
Molyneux, M. E., Taylor, T. E., Wirima, J. J. and Grau, G. E. ( 1991). Tumour necrosis factor, interleukin-6, and malaria. Lancet 337, 1098.CrossRefGoogle Scholar
Mordue, D. G., Monroy, F., La Regina, M., Dinarello, C. A. and Sibley, L. D. ( 2001). Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. Journal of Immunology 167, 4574–4584.CrossRefGoogle Scholar
Naessens, J., Kitani, H., Nakamura, Y., Yagi, Y., Sekikawa, K. and Iraqi, F. ( 2005). TNF-alpha mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection. Clinical and Experimental Immunology 139, 405–410.CrossRefGoogle Scholar
Olsen, C. H. ( 2003). Review of the use of statistics in infection and immunity. Infection and Immunity 71, 6689–6692.CrossRefGoogle Scholar
Omer, F. M., de Souza, J. B. and Riley, E. M. ( 2003). Differential induction of TGF-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. Journal of Immunology 171, 5430–5436.CrossRefGoogle Scholar
Rice, W. R. and Gaines, S. D. ( 1994). Extending nondirectional heterogeneity tests to evaluate simply ordered alternative hypotheses. Proceedings of the National Academy of Sciences, USA 91, 225–226.CrossRefGoogle Scholar
Ritter, U., Mattner, J., Rocha, J. S., Bogdan, C. and Korner, H. ( 2004). The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain. Microbes and Infection 6, 559–565.CrossRefGoogle Scholar
Sam, H. and Stevenson, M. M. ( 1999). Early IL-12 p70, but not p40, production by splenic macrophages correlates with host resistance to blood-stage Plasmodium chabaudi AS malaria. Clinical and Experimental Immunology 117, 343–349.CrossRefGoogle Scholar
Sam, H., Su, Z. and Stevenson, M. M. ( 1999). Deficiency in tumor necrosis factor alpha activity does not impair early protective Th1 responses against blood-stage malaria. Infection and Immunity 67, 2660–2664.Google Scholar
Seixas, E., Cross, C., Quin, S. and Langhorne, J. ( 2001). Direct activation of dendritic cells by the malaria parasite, Plasmodium chabaudi chabaudi. European Journal of Immunology 31, 2970–2978.3.0.CO;2-S>CrossRefGoogle Scholar
Snow, R. W., Guerra, C. A., Noor, A. M., Myint, H. Y. and Hay, S. I. ( 2005). The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, London 434, 214–217.CrossRefGoogle Scholar
Stevenson, M. M., Huang, D. Y., Podoba, J. E. and Nowotarski, M. E. ( 1992). Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL/6 and susceptible A/J mice. Infection and Immunity 60, 1193–1201.Google Scholar
Stevenson, M. M. and Riley, E. M. ( 2004). Innate immunity to malaria. Nature Review, Immunology 4, 169–180.CrossRefGoogle Scholar
Stevenson, M. M. and Tam, M. F. ( 1993). Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clinical and Experimental Immunology 92, 77–83.CrossRefGoogle Scholar
Stevenson, M. M., Tam, M. F., Wolf, S. F. and Sher, A. ( 1995). IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. Journal of Immunology 155, 2545–2556.Google Scholar
Su, Z. and Stevenson, M. M. ( 2002). IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. Journal of Immunology 168, 1348–1355.CrossRefGoogle Scholar
Torre, D., Speranza, F. and Martegani, R. ( 2002). Role of proinflammatory and anti-inflammatory cytokines in the immune response to Plasmodium falciparum malaria. Lancet Infectious Diseases 2, 719–720.CrossRefGoogle Scholar
Waki, S., Uehara, S., Kanbe, K., Ono, K., Suzuki, M. and Nariuchi, H. ( 1992). The role of T cells in pathogenesis and protective immunity to murine malaria. Immunology 75, 646–651.Google Scholar
Walliker, D., Carter, R. and Morgan, S. ( 1971). Genetic recombination in malaria parasites. Nature, London 232, 561–562.CrossRefGoogle Scholar