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Use of an optimality model to solve the immunological puzzle of concomitant infection

Published online by Cambridge University Press:  08 June 2007

A. L. GRAHAM
Affiliation:
318 Corson Hall, Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York 14853, U.S.A.

Abstract

Immunological data indicate that different subsets of T-helper cells work best against different types of infection. Concomitant infection of a host may thus impose either conflicting or synergistic immune response requirements, depending upon the extent to which the component optimal immune responses differ. Drawing upon empirically-determined optimal responses to single-species infections, an optimality model is here used to generate testable hypotheses for optimal responses to concomitant infection. The model is based upon the principle that the joint immune response will minimize divergence from each of the optima for single-species infections, but that it will also be weighted by the importance of mounting the correct response against each infectious organism. The model thus predicts a weighted average response as the optimal response to concomitant infection. Data on concomitant infection of murine hosts by the parasites Schistosoma mansoni and Toxoplasma gondii will provide the first test of the optimality model. If the weighted average hypothesis holds true, then there are no emergent immunological properties of concomitant infections and we may be able to understand immune responses to concomitant infection directly via our understanding of single-species infections.

Type
Research Article
Copyright
© 2002 Cambridge University Press

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References

ALLEN, J. E. & MAIZELS, R. M. (1997). Th1–Th2: reliable paradigm or dangerous dogma? Immunology Today 18, 387392.Google Scholar
BRUNET, L. R., DUNNE, D. W. & PEARCE, E. J. (1998). Cytokine interaction and immune responses during Schistosoma mansoni infection. Parasitology Today 14, 422427.CrossRefGoogle Scholar
CURRY, A. J., ELSE, K. J., JONES, F., BANCROFT, A., GRENCIS, R. K. & DUNNE, D. W. (1995). Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris. Journal of Experimental Medicine 181, 769774.CrossRefGoogle Scholar
DENKERS, E. Y. & GAZZINELLI, R. T. (1998). Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clinical Microbiology Reviews 11, 569588.Google Scholar
FISHMAN, M. A. & PERELSON, A. S. (1999). Th1/Th2 differentiation and cross-regulation. Bulletin of Mathematical Biology 61, 403436.CrossRefGoogle Scholar
INFANTE-DUARTE, C. & KAMRADT, T. (1999). Th1/Th2 balance in infection. Springer Seminars in Immunopathology 21, 317338.CrossRefGoogle Scholar
JANEWAY, C. A., TRAVERS, P., WALPORT, M. & CAPRA, J. D. (1999). Immunobiology: The Immune System in Health and Disease, New York. Elsevier Science, Ltd./Garland Publishing, Inc.Google Scholar
MARSHALL, A. J., BRUNET, L. R., VAN GESSEL, Y., ALCARAZ, A., BLISS, S. K., PEARCE, E. J. & DENKERS, E. Y. (1999). Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-alpha and early death in C57BL/6 mice. Journal of Immunology 163, 20892097.Google Scholar
MOREL, B. F., KALAGNANAM, J. & MOREL, P. A. (1992). Mathematical modeling of Th1–Th2 dynamics. In Theoretical and Experimental Insights into Immunology, Vol. 66 (ed. Perelson, A. S. & Weisbuch, G.), pp. 171190. Berlin, Springer-Verlag.CrossRef
MOSMANN, T. R. & SAD, S. (1996). The expanding universe of T-cell subsets: Th1, Th2 and more. Immunology Today 17, 138146.CrossRefGoogle Scholar
PARKER, G. A. & MAYNARD-SMITH, J. (1990). Optimality theory in evolutionary biology. Nature 348, 2733.CrossRefGoogle Scholar
ROMAGNANI, S. (1996). Th1 and Th2 in human diseases. Clinical Immunology and Immunopathology 80, 225235.CrossRefGoogle Scholar
SCHWEITZER, A. N., SWINTON, J. & ANDERSON, R. M. (1993). Dynamic interaction between Leishmania infection in mice and Th1-type CD4+ T-cells: complexity in outcome without a requirement for Th2-type responses. Parasite Immunology 15, 8599.CrossRefGoogle Scholar
SHER, A. & COFFMAN, R. L. (1992). Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annual Review of Immunology 10, 385409.CrossRefGoogle Scholar