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Optimality analysis of Th1/Th2 immune responses during microparasite-macroparasite co-infection, with epidemiological feedbacks


Individuals are typically co-infected by a diverse community of microparasites (e.g. viruses or protozoa) and macroparasites (e.g. helminths). Vertebrates respond to these parasites differently, typically mounting T helper type 1 (Th1) responses against microparasites and Th2 responses against macroparasites. These two responses may be antagonistic such that hosts face a ‘decision’ of how to allocate potentially limiting resources. Such decisions at the individual host level will influence parasite abundance at the population level which, in turn, will feed back upon the individual level. We take a first step towards a complete theoretical framework by placing an analysis of optimal immune responses under microparasite-macroparasite co-infection within an epidemiological framework. We show that the optimal immune allocation is quantitatively sensitive to the shape of the trade-off curve and qualitatively sensitive to life-history traits of the host, microparasite and macroparasite. This model represents an important first step in placing optimality models of the immune response to co-infection into an epidemiological framework. Ultimately, however, a more complete framework is needed to bring together the optimal strategy at the individual level and the population-level consequences of those responses, before we can truly understand the evolution of host immune responses under parasite co-infection.

Corresponding author
*Corresponding author: Dr A. Fenton, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK. Tel: 0151 795 4473, Fax: 0151 795 4408, Email:
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Abbas A. K., Murphy K. M. and Sher A. (1996). Functional diversity of helper T lymphocytes. Nature 383, 787793.
Anderson R. M. (1980). Depression of host population abundance by direct life-cycle macroparasites. Journal of Theoretical Biology 82, 283311.
Anderson R. M. and May R. M. (1978). Regulation and stability of host-parasite population interactions. I. Regulatory processes. Journal of Animal Ecology 47, 219247.
Anderson R. M. and May R. M. (1981). The population dynamics of microparasites and their invertebrate hosts. Philosophical Transactions of the Royal Society of London, Series B 291, 451524.
Bleay C., Wilkes C. P., Paterson S. and Viney M. E. (2007). Density-dependent immune responses against the gastrointestinal nematode Strongyloides ratti. International Journal for Parasitology 37, 15011509.
Booth M., Vennervald B. J., Kenty L., Butterworth A. E., Kariuki H. C., Kadzo H., Ireri E., Amanga C., Kimani G., Mwatha J. K., Otedo A., Ouma J. H., Muchiri E. and Dunne D. W. (2004). Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and exacerbation of splenomegaly in Kenyan school-aged children. BMC Infection and Disease 4, 13.
Boots M. and Bowers R. G. (1999). Mechanisms of host resistance to microparasites – avoidance, recovery and tolerance – show different evolutionary dynamics. Journal of Theoretical Biology 201, 1323.
Boots M. and Bowers R. G. (2004). The evolution of resistance through costly acquired immunity. Proceedings of the Royal Society of London, Series B 271, 715723.
Bowers R. G. (1999). A baseline model for the apparent competition between many host strains: the evolution of host resistance to microparasites. Journal of Theoretical Biology 200, 6575.
Cox F. E. G. (2001). Concomitant infections, parasites and immune responses. Parasitology 122 (Suppl), S23S38.
Fenton A. (2008). Worms and germs: the population dynamic consequences of microparasite-macroparasite co-infection. Parasitology 135 (in press).
Fishman M. A. and Perelson A. S. (1999). Th1/Th2 differentiation and cross-regulation. Bulletin of Mathematical Biology 61, 403436.
Graham A. L. (2001). Use of an optimality model to solve the immunological puzzle of concomitant infection. Parasitology 122 (Suppl), S61S64.
Graham A. L., Cattadori I. M., Lloyd-Smith J. O., Ferrari M. J. and Bjornstad O. N. (2007). Transmission consequences of co-infection: cytokines writ large? Trends in Parasitology 23, 284291.
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 Disease 191, 410421.
Hotez P. J., Molyneux D. H., Fenwick A., Ottesen E., Ehrlich Sachs S. and Sachs J. D. (2006). Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Medicine 3, e102.
Jameson S. C. (2002). Maintaining the norm: T-cell homeostasis. Nature Reviews in Immunology 2, 547556.
Koski K. G. and Scott M. E. (2001). Gastrointestinal nematodes, nutrition and immunity: breaking the negative spiral. Annual Review of Nutrition 21, 297321.
Lamb T. J., Graham A. L., Le Geoff L. and Allen J. E. (2005). Co-infected C57BL/6 mice mount appropriately polarized and compartmentalized cytokine responses to Litomosoides sigmodontis and Leishmania major but disease progression is altered. Parasite Immunology 27, 317324.
Maizels R. M., Balic A., Gomez-Escobar N., Nair M., Taylor M. D. and Allen J. E. (2004). Helminth parasites--masters of regulation. Immunological Reviews 201, 89116.
May R. M. and Anderson R. M. (1978). Regulation and stability of host-parasite population interactions. II. Destabilizing processes. Journal of Animal Ecology 47, 249267.
May R. M. and Anderson R. M. (1979). Population biology of infectious diseases: Part II. Nature 280, 455461.
McCallum H. and Dobson A. (1995) Detecting disease and parasite threats to endangered species and ecosystems. Trends in Ecology and Evolution 10, 190194.
Medley G. F. (2002). The epidemiological consequences of optimisation of the individual host immune response. Parasitology 125 (Suppl), S61S70.
Miller M. R., White A. and Boots M. (2007). Host life span and the evolution of resistance characteristics. Evolution 61, 214.
Mills K. H. (2004). Regulatory T cells: friend or foe in immunity to infection? Nature Reviews in Immunology 4, 841855.
Page K. R., Scott A. L. and Manabe Y. C. (2006). The expanding realm of heterologous immunity: friend or foe? Cellular Microbiology 8, 185196.
Pedersen A. B. and Fenton A. (2007). Emphasizing the ecology in parasite community ecology. Trends in Ecology and Evolution 22, 133139.
Petney T. N. and Andrews R. H. (1998). Multiparasite communities in animals and humans: Frequency, structure and pathogenic significance. International Journal for Parasitology 28, 377393.
Shparago N., Zelazowski P., Jin L., McIntyre T. M., Stuber E., Pechana L. M., Kehry M. R., Mond J. J., Max E. E. and Snapper C. M. (1996). IL-10 selectively regulates murine Ig isotype switching. International Immunology 8, 781790.
Shudo E. and Iwasa Y. (2001). Inducible defense against pathogens and parasites: optimal choice among multiple options. Journal of Theoretical Biology 209, 233247.
Snapper C. M., Finkleman F. D. and Paul W. E. (1988 a). Regulation of IgG1 and IgE production by interleukin 4. Immunology Reviews 102, 5175.
Snapper C. M., Peschel C. and Paul W. E. (1988 b). IFN-gamma stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. Journal of Immunology 140, 21212127.
Yates A., Bergmann C., Van Hemmen J. L., Stark J. and Callard R. (2000). Cytokine-modulated regulation of helper T cell populations. Journal of Theoretical Biology 206, 539560.
Yates A., Callard R. and Stark J. (2004). Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. Journal of Theoretical Biology 231, 181196.
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