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Integrating immune mechanisms to model nematode worm burden: an example in sheep

Published online by Cambridge University Press:  18 August 2015

ROMAIN GARNIER*
Affiliation:
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA
BRYAN T. GRENFELL
Affiliation:
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA
ALASDAIR J. NISBET
Affiliation:
Moredun Research Institute, Pentlands Science Park, Edinburgh, Scotland, UK
JACQUELINE B. MATTHEWS
Affiliation:
Moredun Research Institute, Pentlands Science Park, Edinburgh, Scotland, UK
ANDREA L. GRAHAM
Affiliation:
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA
*
*Corresponding author. Department of Ecology and Evolutionary Biology, 106A Guyot Hall, Princeton University, Princeton, New Jersey 08544, USA. E-mail: romaing@princeton.edu

Summary

Gastrointestinal nematodes represent important sources of economic losses in farmed ruminants, and the increasing frequency of anthelmintic resistance requires an increased ability to explore alternative strategies. Theoretical approaches at the crossroads of immunology and epidemiology are valuable tools in that context. In the case of Teladorsagia circumcincta in sheep, the immunological mechanisms important for resistance are increasingly well-characterized. However, despite the existence of a wide range of theoretical models, there is no framework integrating the characteristic features of this immune response into a tractable phenomenological model. Here, we propose to bridge that gap by developing a flexible modelling framework that allows for variability in nematode larval intake which can be used to track the variations in worm burdens. We parameterize this model using data from trickle infection of sheep and show that using simple immunological assumptions, our model can capture the dynamics of both adult worm burdens and nematode fecal egg counts. In addition, our analysis reveals interesting dose-dependent effects on the immune response. Finally, we discuss potential developments of this model and highlight how an improved cross-talk between empiricists and theoreticians would facilitate important advances in the study of infectious diseases.

Type
Special Issue Article
Copyright
Copyright © Cambridge University Press 2015 

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References

REFERENCES

Adler, F. and Kretzschmar, M. (1992). Aggregation and stability in parasite – host models. Parasitology 104, 199205.Google Scholar
Allen, J. E. and Maizels, R. M. (2011). Diversity and dialogue in immunity to helminths. Nature Immunology 11, 375388.Google Scholar
Anderson, R. M. and May, R. M. (1978). Regulation and stability of host-parasite population interactions .1. Regulatory processes. Journal of Animal Ecology 47, 219247.Google Scholar
Armour, J. (1980). The epidemiology of helminth disease in farm animals. Veterinary Parasitology 6, 746.Google Scholar
Barger, I. (1999). The role of epidemiological knowledge and grazing management for helminth control in small ruminants. International Journal for Parasitology 29, 4147.Google Scholar
Bishop, S. (2012 a). Possibilities to breed for resistance to nematode parasite infections in small ruminants in tropical production systems. Animal 6, 741747.Google Scholar
Bishop, S. C. (2012 b). A consideration of resistance and tolerance for ruminant nematode infections. Frontiers in Genetics 3, 168.Google Scholar
Campbell, S., Siegel, M. and Knowlton, B. J. (1977). Sheep immunoglobulins and their transmission to the neonatal lamb. New Zealand Veterinary Journal 25, 361365.Google Scholar
Cornell, S. (2005). Modelling nematode populations: 20 years of progress. Trends in Parasitology 21, 542545.Google Scholar
Craig, B., Pilkington, J. and Pemberton, J. (2006). Gastrointestinal nematode species burdens and host mortality in a feral sheep population. Parasitology 133, 485496.CrossRefGoogle Scholar
Ellis, S., Matthews, J. B., Shaw, D. J., Paterson, S., McWilliam, H. E., Inglis, N. F. and Nisbet, A. J. (2014). Ovine IgA-reactive proteins from Teladorsagia circumcincta infective larvae. International Journal for Parasitology 44, 743750.CrossRefGoogle ScholarPubMed
Epe, C. and Kaminsky, R. (2013). New advancement in anthelmintic drugs in veterinary medicine. Trends in Parasitology 29, 129134.Google Scholar
Falzon, L., O'Neill, T., Menzies, P., Peregrine, A., Jones-Bitton, A. and Mederos, A. (2014). A systematic review and meta-analysis of factors associated with anthelmintic resistance in sheep. Preventive Veterinary Medicine 117, 388402.Google Scholar
Gaba, S., Gruner, L. and Cabaret, J. (2006). The establishment rate of a sheep nematode: revisiting classics using a meta-analysis of 87 experiments. Veterinary Parasitology 140, 302311.Google Scholar
Galvani, A. P. (2003). Immunity, antigenic heterogeneity, and aggregation of helminth parasites. Journal of Parasitology 89, 232241.Google Scholar
Garnier, R. and Graham, A. L. (2014). Insights from parasite-specific serological tools in eco-immunology. Integrative and Comparative Biology 54, 363376.Google Scholar
Gibbs, H. C. (1986). Hypobiosis in parasitic nematodes – an update. Advances in Parasitology 25, 129174.Google Scholar
Gimenez, O., Abadi, F., Barnagaud, J. Y., Blanc, L., Buoro, M., Cubaynes, S., Desprez, M., Gamelon, M., Guilhaumon, F. and Lagrange, P. (2013). How can quantitative ecology be attractive to young scientists? Balancing computer/desk work with fieldwork. Animal Conservation 16, 134136.Google Scholar
Gossner, A. G., Venturina, V. M., Shaw, D. J., Pemberton, J. M. and Hopkins, J. (2012). Relationship between susceptibility of Blackface sheep to Teladorsagia circumcincta infection and an inflammatory mucosal T cell response. Veterinary Research 43, 26.Google Scholar
Gourbière, S., Morand, S. and Waxman, D. (2015). Fundamental Factors Determining the Nature of Parasite Aggregation in Hosts. PLoS ONE 10, e0116893.Google Scholar
Grenfell, B., Dietz, K. and Roberts, M. (1995 a). Modelling the immuno-epidemiology of macroparasites in naturally-fluctuating host populations. In Ecology of Infectious Diseases in Natural Populations (ed. Grenfell, B. T. and Dobson, A. P.), pp. 362383. Cambridge University Press, Cambridge, UK.CrossRefGoogle Scholar
Grenfell, B. T., Wilson, K., Isham, V. S., Boyd, H. E. G. and Dietz, K. (1995 b). Modelling patterns of parasite aggregation in natural populations: trichostrongylid nematode-ruminant interactions as a case study. Parasitology 111, S135S151.Google Scholar
Gulland, F. M. D. (1992). The role of nematode parasites in Soay sheep (Ovis aries L.) mortality during a population crash. Parasitology 105, 493503.Google Scholar
Guthrie, A., Learmount, J., VanLeeuwen, J., Peregrine, A., Kelton, D., Menzies, P., Fernández, S., Martin, R., Mederos, A. and Taylor, M. (2010). Evaluation of a British computer model to simulate gastrointestinal nematodes in sheep on Canadian farms. Veterinary Parasitology 174, 92105.CrossRefGoogle ScholarPubMed
Halliday, A., Routledge, C., Smith, S., Matthews, J. and Smith, W. (2007). Parasite loss and inhibited development of Teladorsagia circumcincta in relation to the kinetics of the local IgA response in sheep. Parasite Immunology 29, 425434.Google Scholar
Hayward, A. D., Garnier, R., Watt, K. A., Pilkington, J. G., Grenfell, B. T., Matthews, J. B., Pemberton, J. M., Nussey, D. H. and Graham, A. L. (2014). Heritable, heterogeneous and costly resistance of sheep against nematodes and potential feedbacks to epidemiological dynamics. American Naturalist 184, S58S76.Google Scholar
Hellriegel, B. (2001). Immuno-epidemiology–bridging the gap between immunology and epidemiology. Trends in Parasitology 17, 102106.Google Scholar
Henderson, N. G. and Stear, M. J. (2006). Eosinophil and IgA responses in sheep infected with Teladorsagia circumcincta . Veterinary Immunology and Immunopathology 112, 6266.Google Scholar
Hong, C., Michel, J. and Lancaster, M. (1986). Populations of Ostertagia circumcincta in lambs following a single infection. International Journal for Parasitology 16, 6367.Google Scholar
Hong, C., Michel, J. F. and Lancaster, M. B. (1987). Observations on the dynamics of worm burdens in lambs infected daily with Ostertagia circumcincta . International Journal for Parasitology 17, 951956.Google Scholar
Isham, V. (1991). Assessing the variability of stochastic epidemics. Mathematical Biosciences 107, 209224.Google Scholar
Isham, V. (1995). Stochastic models of host-macroparasite interaction. Annals of Applied Probability 720740.Google Scholar
Kao, R., Leathwick, D., Roberts, M. and Sutherland, I. (2000). Nematode parasites of sheep: a survey of epidemiological parameters and their application in a simple model. Parasitology 121, 85103.Google Scholar
Kretzschmar, M. and Adler, F. (1993). Aggregated distributions in models for patchy populations. Theoretical Population Biology 43, 130.Google Scholar
Learmount, J., Taylor, M., Smith, G. and Morgan, C. (2006). A computer model to simulate control of parasitic gastroenteritis in sheep on UK farms. Veterinary Parasitology 142, 312329.Google Scholar
Learmount, J., Taylor, M. and Bartram, D. (2012). A computer simulation study to evaluate resistance development with a derquantel–abamectin combination on UK sheep farms. Veterinary Parasitology 187, 244253.Google Scholar
Lessler, J., Edmunds, W. J., Halloran, M. E., Hollingsworth, T. D. and Lloyd, A. L. (2015). Seven challenges for model-driven data collection in experimental and observational studies. Epidemics 10, 7882.Google Scholar
Mair, C., Matthews, L., Prada, J., De Cisneros, J., Stefan, T. and Stear, M. J. (2015). Multitrait indices to predict worm length and number in sheep with natural, mixed predominantly Teladorsagia circumcincta infection. Parasitology 142, 773782.Google Scholar
McRae, K. M., Good, B., Hanrahan, J. P., Glynn, A., O'Connell, M. J. and Keane, O. M. (2014). Response to Teladorsagia circumcincta infection in Scottish Blackface lambs with divergent phenotypes for nematode resistance. Veterinary Parasitology 206, 200207.Google Scholar
Morgan, E. and Van Dijk, J. (2012). Climate and the epidemiology of gastrointestinal nematode infections of sheep in Europe. Veterinary Parasitology 189, 814.CrossRefGoogle ScholarPubMed
Nieuwhof, G. J. and Bishop, S. C. (2005). Costs of the major endemic diseases of sheep in Great Britain and the potential benefits of reduction in disease impact. Animal Science 81, 2329.Google Scholar
Nisbet, A., Bell, N., McNeilly, T., Knox, D., Maizels, R., Meikle, L., Wildblood, L. and Matthews, J. (2010). A macrophage migration inhibitory factor-like tautomerase from Teladorsagia circumcincta (Nematoda: Strongylida). Parasite Immunology 32, 503511.Google Scholar
Nisbet, A. J., McNeilly, T. N., Wildblood, L. A., Morrison, A. A., Bartley, D. J., Bartley, Y., Longhi, C., McKendrick, I. J., Palarea-Albaladejo, J. and Matthews, J. B. (2013). Successful immunization against a parasitic nematode by vaccination with recombinant proteins. Vaccine 31, 40174023.Google Scholar
Nussey, D. H., Watt, K. A., Clark, A., Pilkington, J. G., Pemberton, J. M., Graham, A. L. and McNeilly, T. N. (2014). Multivariate immune defences and fitness in a wild mammal: complex but ecologically important associations among different plasma antibodies, host health and survival. Proceedings of the Royal Society of London Series B-Biological Sciences 281, 20132931.Google Scholar
Pfeffer, A., Shaw, R., Green, R. and Phegan, M. (2005). The transfer of maternal IgE and other immunoglobulins specific for Trichostrongylus colubriformis larval excretory/secretory product to the neonatal lamb. Veterinary Immunology and Immunopathology 108, 315323.Google Scholar
Prada Jiménez de Cisneros, J., Matthews, L., Mair, C., Stefan, T. and Stear, M. J. (2014 a). The transfer of IgA from mucus to plasma and the implications for diagnosis and control of nematode infections. Parasitology 141, 875879.Google Scholar
Prada Jiménez de Cisneros, J., Stear, M. J., Mair, C., Singleton, D., Stefan, T., Stear, A., Marion, G. and Matthews, L. (2014 b). An explicit immunogenetic model of gastrointestinal nematode infection in sheep. Journal of the Royal Society Interface 11, 20140416.Google Scholar
Restif, O., Hayman, D. T., Pulliam, J. R., Plowright, R. K., George, D. B., Luis, A. D., Cunningham, A. A., Bowen, R. A., Fooks, A. R. and O'Shea, T. J. (2012). Model-guided fieldwork: practical guidelines for multidisciplinary research on wildlife ecological and epidemiological dynamics. Ecology Letters 15, 10831094.CrossRefGoogle ScholarPubMed
Saddiqi, H., Sarwar, M., Iqbal, Z., Nisa, M. and Shahzad, M. (2012). Markers/parameters for the evaluation of natural resistance status of small ruminants against gastrointestinal nematodes. Animal 6, 9941004.Google Scholar
Sargison, N. D. (2013). Understanding the epidemiology of gastrointestinal parasitic infections in sheep: what does a faecal helminth egg count tell us? Small Ruminant Research 110, 7881.Google Scholar
Shaw, D. J., Grenfell, B. T. and Dobson, A. P. (1998). Patterns of macroparasite aggregation in wildlife host populations. Parasitology 117, 597610.Google Scholar
Shaw, R., Pfeffer, A. and Bischof, R. (2009). Ovine IgE and its role in immunological protection and disease. Veterinary Immunology and Immunopathology 132, 3140.Google Scholar
Shaw, R., Morris, C., Wheeler, M., Tate, M. and Sutherland, I. (2012). Salivary IgA: a suitable measure of immunity to gastrointestinal nematodes in sheep. Veterinary Parasitology 186, 109117.Google Scholar
Singleton, D. R., Stear, M. J. and Matthews, L. (2011). A mechanistic model of developing immunity to Teladorsagia circumcincta infection in lambs. Parasitology 138, 322332.Google Scholar
Smith, G. and Galligan, D. T. (1988). Mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta, and the economic evaluation of disease control strategies. Veterinary Parasitology 27, 7383.Google Scholar
Smith, S., Nisbet, A., Meikle, L., Inglis, N., Sales, J., Beynon, R. and Matthews, J. (2009). Proteomic analysis of excretory/secretory products released by Teladorsagia circumcincta larvae early post-infection. Parasite Immunology 31, 1019.Google Scholar
Smith, W. (2007). Some observations on immunologically mediated inhibited Teladorsagia circumcincta and their subsequent resumption of development in sheep. Veterinary Parasitology 147, 103109.Google Scholar
Smith, W., Jackson, F., Jackson, E. and Williams, J. (1983 a). Local immunity and Ostertagia circumcincta: changes in the gastric lymph of sheep after a primary infection. Journal of Comparative Pathology 93, 471478.CrossRefGoogle ScholarPubMed
Smith, W., Jackson, F., Jackson, E. and Williams, J. (1983 b). Local immunity and Ostertagia circumcingta: changes in the gastric lymph of immune sheep after a challenge infection. Journal of Comparative Pathology 93, 479488.Google Scholar
Smith, W., Jackson, F., Jackson, E., Williams, J. and Miller, H. (1984). Manifestations of resistance to ovine ostertagiasis associated with immunological responses in the gastric lymph. Journal of Comparative Pathology 94, 591601.Google Scholar
Stear, M., Bishop, S., Doligalska, M., Duncan, J., Holmes, P., Irvine, J., McCririe, L., McKellar, Q., Sinski, E. and Murray, M. (1995). Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta . Parasite Immunology 17, 643652.Google Scholar
Stear, M., Bishop, S., Henderson, N. and Scott, I. (2003). A key mechanism of pathogenesis in sheep infected with the nematode Teladorsagia circumcincta . Animal Health Research Reviews 4, 4552.Google Scholar
Stear, M. J. and Bishop, S. C. (1999). The curvi-linear relationship between worm length and fecundity of Teladorsagia circumcincta . International Journal for Parasitology 29, 777780.Google Scholar
Venturina, V. M., Gossner, A. G. and Hopkins, J. (2013). The immunology and genetics of resistance of sheep to Teladorsagia circumcincta . Veterinary Research Communications 37, 171181.Google Scholar
Wilson, K., Grenfell, B. T., Pilkington, J. G., Boyd, H. E. G. and Gulland, F. M. D. (2004). Parasites and their impact. In Soay Sheep. Dynamics and Selection in an Island Population (ed. Clutton-Brock, T. and Pemberton, J.), pp. 113165. Cambridge University Press, Cambridge, UK.Google Scholar
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