Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-26T08:04:20.489Z Has data issue: false hasContentIssue false

Measuring immune system variation to help understand host-pathogen community dynamics

Published online by Cambridge University Press:  27 March 2008

J. E. BRADLEY*
Affiliation:
School of Biology, University of Nottingham, Nottingham NG7 2RD, UK
J. A. JACKSON
Affiliation:
School of Biology, University of Nottingham, Nottingham NG7 2RD, UK
*
*Corresponding author: School of Biology, University of Nottingham, Nottingham NG7 2RD, UK. Tel: +44 (0)115 951 3207. Fax: +44 (0)115 951 3251. E-mail: [email protected]

Summary

Carefully chosen immunological measurements, informed by recent advances in our understanding of the diversity and control of immune mechanisms, can add great interpretative value to ecological studies of infection. This is especially so for co-infection studies, where interactions between species are often mediated via the host's immune response. Here we consider how immunological measurements can strengthen inference in different types of co-infection analysis. In particular, we identify how measuring immune response variables in field studies can help reveal inter-species interactions otherwise obscured by confounding processes operating on count or prevalence data. Furthermore, we suggest that, due to the difficulty of quantifying microbial pathogen communities in field studies, innate responses against broad pathogen types (mediated by pattern response receptors) may be useful quantitative markers of exposure to bacteria and viruses. An ultimate goal of ecological co-infection studies may also be to understand how dynamics within host-parasite assemblages emerge from trade-offs involving different arms of the immune system. We reflect on the phenotypic measures that might best represent levels of responsiveness and bias in immune function. These include mediators associated with different T-helper cell subsets and innate responses controlled by pattern response receptors, such as the Toll-like receptors (TLRs).

Type
Original Articles
Copyright
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Babu, S., Blauvelt, C. P., Kumaraswami, V. and Nutman, T. B. (2006). Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. Journal of Immunology 176, 32483256.CrossRefGoogle ScholarPubMed
Bajer, A., Behnke, J. M., Pawelczyk, A., Kulis, K., Sereda, M. J. and Sinski, E. (2005). Medium-term temporal stability of the helminth component community structure in bank voles (Clethrionomys glareolus) from the Mazury Lake District region of Poland. Parasitology 130, 213228.CrossRefGoogle ScholarPubMed
Behnke, J. M., Bajer, A., Sinski, E. and Wakelin, D. (2001 a). Interactions involving intestinal nematodes of rodents experimental and field studies. Parasitology 122, S39S49.CrossRefGoogle ScholarPubMed
Behnke, J. M., Barnard, C. J., Bajer, A., Bray, D., Dinmore, J., Frake, K., Osmond, J., Race, T. and Sinski, E. (2001 b). Variation in the helminth community structure in bank voles (Clethrionomys glareolus) from three comparable localities in the Mazury Lake District region of Poland. Parasitology 123, 401414.CrossRefGoogle ScholarPubMed
Behnke, J. M., Gilbert, F. S., Abu-Madi, M. A. and Lewis, J. W. (2005). Do the helminth parasites of wood mice interact Journal of Animal Ecology 74, 982993.CrossRefGoogle Scholar
Behnke, J. M., Harris, P. D., Bajer, A., Barnard, C. J., Sherif, N., Cliffe, L., Hurst, J., Lamb, M., Rhodes, A., James, M., Clifford, S., Gilbert, F. S. and Zalat, S. (2004). Variation in the helminth community structure in spiny mice (Acomys dimidiatus) from four montane wadis in the St Katherine region of the Sinai Peninsula in Egypt. Parasitology 129, 379398.CrossRefGoogle ScholarPubMed
Behnke, J. M., Wakelin, D. and Wilson, M. M. (1978). Trichinella spiralis: delayed rejection in mice concurrently infected with Nematospiroides dubius. Experimental Parasitology 46, 121130.CrossRefGoogle ScholarPubMed
Bluestone, J. A. and Abbas, A. K. (2003). Natural versus adaptive regulatory T cells. Nature Reviews in Immunology 3, 253257.CrossRefGoogle ScholarPubMed
Booth, M. (2006). The role of residential location in apparent helminth and malaria associations. Trends in Parasitology 22, 359362.CrossRefGoogle ScholarPubMed
Booth, M. and Dunne, D. W. (2004). Spatial awareness in parasite immuno-epidemiology. Parasite Immunology 26, 499507.CrossRefGoogle ScholarPubMed
Booth, M., Mwatha, J. K., Joseph, S., Jones, F. M., Kadzo, H., Ireri, E., Kazibwe, F., Kemijumbi, J., Kariuki, C., Kimani, G., Ouma, J. H., Kabatereine, N. B., Vennervald, B. J. and Dunne, D. W. (2004). Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-γ, high TNF-α, or low RANTES, depending on age and gender. Journal of Immunology 172, 12951303.CrossRefGoogle ScholarPubMed
Bosisio, D., Polentarutti, N., Sironi, M., Bernasconi, S., Miyake, K., Webb, G. R., Martin, M. U., Mantovani, A. and Muzio, M. (2002). Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 99, 34273431.CrossRefGoogle ScholarPubMed
Bottomley, C., Isham, V. and Basanez, M. G. (2005). Population biology of multispecies helminth infection: interspecific interactions and parasite distribution. Parasitology 131, 417433.CrossRefGoogle ScholarPubMed
Bourhis, L. L. and Werts, C. (2007). Role of Nods in bacterial infection. Microbes and Infection 9, 629636.CrossRefGoogle ScholarPubMed
Brown, M., Mawa, P. A., Kaleebu, P. and Elliott, A. M. (2006). Helminths and HIV infection: epidemiological observations on immunological hypotheses. Parasite Immunology 28, 613623.CrossRefGoogle ScholarPubMed
Cattadori, I. M., Albert, R. and Boag, B. (2007). Variation in host susceptibility and infectiousness generated by co-infection: the myxoma-Trichostrongylus retortaeformis case in wild rabbits. Journal of the Royal Society Interface 4, 831840.CrossRefGoogle ScholarPubMed
Chen, W., Jin, W., Hardegen, N., Lei, K.-J., Li, L., Marinos, N., McGrady, G. and Wahl, S. M. (2003). Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. Journal of Experimental Medicine 198, 18751886.CrossRefGoogle ScholarPubMed
Christensen, N. O., Nansen, P., Fagbemi, B. O. and Monrad, J. (1987). Heterologous antagonistic and synergistic interactions between helminths and between helminths and protozoans in concurrent experimental infection of mammalian hosts. Parasitology Research 73, 387410.CrossRefGoogle ScholarPubMed
Cliffe, L. J. and Grencis, R. K. (2004). The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Advances in Parasitology 57, 255307.CrossRefGoogle ScholarPubMed
Cooper, P. J., Chico, M., Sandoval, C., Espinel, I., Guevara, A., Levine, M. M., Griffin, G. E. and Nutman, T. B. (2001). Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Infection and Immunity 69, 15741580.CrossRefGoogle ScholarPubMed
De Maeyer, E. and De Maeyer-Guignard, J. (1998). Type I interferons. International Reviews of Immunology 17, 5373.CrossRefGoogle ScholarPubMed
Diaz, A. and Allen, J. E. (2007). Mapping immune response profiles: the emerging scenario from helminth immunology. European Journal of Immunology 37, 33193326.CrossRefGoogle ScholarPubMed
Ege, M. J., Bieli, C., Frei, R., van Strien, R. T., Riedler, J., Üblagger, E., Schram-Bijkerk, D., Brunekreef, B., van Hage, M., Scheynius, A., Pershagen, G., Benz, M. R., Lauener, R., von Mutius, E., Braun-Fahrländer, C. and the PARSIFAL Study team. (2006). Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. Journal of Allergy and Clinical Immunology 117, 817823.CrossRefGoogle Scholar
Elias, D., Wolday, D., Akuffo, H., Petros, B., Bronner, U. and Britton, S. (2001). Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination. Clinical and Experimental Immunology 123, 219225.CrossRefGoogle Scholar
Elliott, D. E., Setiawan, T., Metwali, A., Blum, A., Urban, J. F. Jr. and Weinstock, J. V. (2004). Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. European Journal of Immunology 34, 26902698.CrossRefGoogle ScholarPubMed
Esch, G. W., Bush, A. O. and Aho, J. M. (1990). Parasite Communities: Patterns and Processes. Chapman and Hall, New York.Google Scholar
Fast, M. D., Johnson, S. C. and Jones, S. R. M. (2007). Differential expression of the pro-inflammatory cytokines IL-1β-1, TNFα-1 and IL-8 in vaccinated pink (Oncorhynchus gorbuscha) and chum (Oncorhynchus keta) salmon juveniles. Fish and Shellfish Immunology 22, 403407.CrossRefGoogle ScholarPubMed
Faulkner, H., Gardon, J., Kamgno, J., Enyong, P., Boussinesq, M. and Bradley, J. E. (2001). Antibody responses in onchocerciasis as a function of age and infection intensity. Parasite Immunology 23, 509516.CrossRefGoogle ScholarPubMed
Faulkner, H., Turner, J., Behnke, J., Kamgno, J., Rowlinson, M. C., Bradley, J. E. and Boussinesq, M. (2005). Associations between filarial and gastrointestinal nematodes. Transactions of the Royal Society of Tropical Medicine and Hygiene 99, 301312.CrossRefGoogle ScholarPubMed
Finkelman, F. D., Katona, I. M., Mosmann, T. R., Coffman, R. L. (1988). IFN-γ regulates the isotypes of Ig secreted during in vivo humoral immune responses. Journal of Immunology 140, 10221027.CrossRefGoogle ScholarPubMed
Finney, C. A., Taylor, M. D., Wilson, M. S. and Maizels, R. M. (2007). Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection. European Journal of Immunology 37, 18741886.CrossRefGoogle ScholarPubMed
Gause, W. C., Urban, J. F. and Stadecker, M. J. (2003). The immune response to parasitic helminths: insights from murine models. Trends in Immunology 24, 269277.CrossRefGoogle ScholarPubMed
Goüy de Bellocq, J., Porcherie, A., Moulia, C. and Morand, S. (2007). Immunocompetence does not correlate with resistance to helminth parasites in house mouse subspecies and their hybrids. Parasitology Research 100, 321328.CrossRefGoogle Scholar
Graham, A. L., Cattadori, I. M., Lloyd-Smith, J. O., Ferrari, M. J. and Bjornstad, O. N. (2007). Transmission consequences of coinfection: cytokines writ large Trends in Parasitology 23, 284291.CrossRefGoogle ScholarPubMed
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, 410421.CrossRefGoogle ScholarPubMed
Grogan, J. L., Kremsner, P. G., Deelder, A. M. and Yazdanbakhsh, M. (1998). Antigen-specific proliferation and interferon-gamma and interleukin-5 production are down-regulated during Schistosoma haematobium infection. Journal of Infectious Diseases 177, 14331437.CrossRefGoogle ScholarPubMed
Guillot, L., Le Goffic, R., Bloch, S., Escriou, N., Akira, S., Chignard, M. and Si-Tahar, M. (2005). Involvement of Toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. Journal of Biological Chemistry 280, 55715580.CrossRefGoogle ScholarPubMed
Holmes, J. C. (1961). Effects of concurrent infections on Hymenolepis diminuta (Cestoda) and Moniliformis dubius (Acanthocephala). I. General effects and comparison with crowding. Journal of Parasitology 47, 209216.CrossRefGoogle ScholarPubMed
Huggett, J., Dheda, K., Bustin, S. and Zumla, A. (2005). Real-time RT-PCR normalisation; strategies and considerations. Genes and Immunity 6, 279284.CrossRefGoogle ScholarPubMed
Ince, M. N., Elliott, D. E., Setiawan, T., Blum, A., Metwali, A., Wang, Y., Urban, J. F. Jr. and Weinstock, J. V. (2006). Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFβ after lipopolysaccharide stimulation. Journal of Immunology 176, 726729.CrossRefGoogle ScholarPubMed
Ing, R., Su, Z., Scott, M. E. and Koski, K. G. (2000). Suppressed T helper 2 immunity and prolonged survival of a nematode parasite in protein-malnourished mice. Proceedings of the National Academy of Sciences, USA 97, 70787083.CrossRefGoogle ScholarPubMed
Jackson, J. A., Pleass, R. J., Cable, J., Bradley, J. E. and Tinsley, R. C. (2006 a). Heterogenous interspecific interactions in a host-parasite system. International Journal for Parasitology 36, 13411349.CrossRefGoogle Scholar
Jackson, J. A. and Tinsley, R. C. (2007). Evolutionary diversity in polystomatids infecting tetraploid and octoploid Xenopus in East African highlands: biological and molecular evidence. Parasitology 134, 12231235.CrossRefGoogle ScholarPubMed
Jackson, J. A., Tinsley, R. C. and Hinkel, H. H. (1998). Mutual exclusion of congeneric monogenean species in a space-limited habitat. Parasitology 117, 563569.CrossRefGoogle Scholar
Jackson, J. A., Turner, J. D., Kamal, M., Wright, V., Bickle, Q., Else, K. J., Ramsan, M. and Bradley, J. E. (2006 b). Gastrointestinal nematode infection is associated with variation in innate immune responsiveness. Microbes and Infection 8, 487492.CrossRefGoogle ScholarPubMed
Jackson, J. A., Turner, J. D., Rentoul, L., Faulkner, H., Behnke, J. M., Hoyle, M., Grencis, R. K., Else, K. J., Kamgno, J., Boussinesq, M. and Bradley, J. E. (2004 a). T helper cell type 2 responsiveness predicts future susceptibility to gastrointestinal nematodes in humans. Journal of Infectious Diseases 190, 18041811.CrossRefGoogle ScholarPubMed
Jackson, J. A., Turner, J. D., Rentoul, L., Faulkner, H., Behnke, J. M., Hoyle, M., Grencis, R. K., Else, K. J., Kamgno, J., Bradley, J. E. and Boussinesq, M. (2004 b). Cytokine response profiles predict species-specific infection patterns in human GI nematodes. International Journal for Parasitology 34, 12371244.CrossRefGoogle ScholarPubMed
Janeway, C. A. and Medzhitov, R. (2002). Innate immune recognition. Annual Review of Immunology 20, 197216.CrossRefGoogle ScholarPubMed
Janeway, C. A., Travers, P., Walport, M. and Shlomchik, M. J. (2006). Immunobiology. Garland Publishing, New York.Google Scholar
Janovy, J. Jr.Clopton, R. E. and Percival, T. J. (1992). The roles of ecological and evolutionary influences in providing structure to parasite species assemblages. Journal of Parasitology 78, 630640.CrossRefGoogle ScholarPubMed
Jiang, H. and Chess, L. (2004). An integrated view of suppressor T cell subsets in immunoregulation. Journal of Clinical Investigation 114, 11981208.CrossRefGoogle ScholarPubMed
Kennedy, M. W. and Nager, R. G. (2006). The perils and prospects of using phytohaemagglutinin in evolutionary ecology. Trends in Ecology and Evolution 21, 653655.CrossRefGoogle ScholarPubMed
Koski, K. G. and Scott, M. E. (2001). Gastrointestinal nematodes, nutrition and immunity: breaking the negative spiral. Annual Review of Nutrition 21, 297321.CrossRefGoogle ScholarPubMed
Lamb, T. J., Graham, A. L., Le Goff, 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.CrossRefGoogle ScholarPubMed
Lauener, R. P., Birchler, T., Adamski, J., Braun-Fahrländer, C., Bufe, A., Herz, U., von Mutius, E., Nowak, D., Riedler, J., Waser, M., Sennhauser, F. H. and the ALEX study group. (2002). Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. The Lancet 360, 465466.CrossRefGoogle ScholarPubMed
Layland, L. E., Rad, R., Wagner, H. and Prazeres da Costa, C. U. (2007). Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. European Journal of Immunology 37, 21742184.CrossRefGoogle ScholarPubMed
Legendre, P. and Gallagher, E. D. (2001). Ecologically meaningful transformations for ordination of species data. Oecologia 129, 271280.CrossRefGoogle ScholarPubMed
Lello, J., Boag, B., Fenton, A., Stevenson, I. R. and Hudson, P. J. (2004). Competition and mutualism among the gut helminths of a mammalian host. Nature 428, 840844.CrossRefGoogle ScholarPubMed
Li, J.-H., Shao, J.-Z., Xiang, L.-X. and Wen, Y. (2007). Cloning, characterization and expression analysis of pufferfish interleukin-4 cDNA: The first evidence of Th2-type cytokine in fish. Molecular Immunology 44, 20782086.CrossRefGoogle ScholarPubMed
Long, K. Z. and Nanthakumar, N. (2004). Energetic and nutritional regulation of the adaptive immune response and trade-offs in ecological immunology. American Journal of Human Biology 16, 499507.CrossRefGoogle ScholarPubMed
Lotz, J. M. and Font, W. F. (1994). Excess positive associations in communities of intestinal helminths of bats: a refined null hypothesis and a test of the facilitation hypothesis. Journal of Parasitology 80, 398413.CrossRefGoogle Scholar
Maniero, G. D. and Carey, C. (1997). Changes in selected aspects of immune function in the leopard frog, Rana pipiens, associated with exposure to cold. Journal of Comparative Physiology B 167, 256263.CrossRefGoogle ScholarPubMed
Martin, L. B. 2nd, Navara, K. J., Weil, Z. M. and Nelson, R. J. (2007 b). Immunological memory is compromised by food restriction in deer mice Peromyscus maniculatus. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 292, R316R320.CrossRefGoogle ScholarPubMed
Martin, L. B., Pless, M., Svoboda, J. and Wikelski, M. (2004). Immune activity in temperate and tropical house sparrows: A common-garden experiment. Ecology 85, 23232331.CrossRefGoogle Scholar
Martin, L. B., Weil, Z. M. and Nelson, R. J. (2006). Refining approaches and diversifying directions in ecoimmunology. Integrative and Comparative Biology 46, 10301039.CrossRefGoogle ScholarPubMed
Martin, L. B., Weil, Z. M. and Nelson, R. J. (2007 a). Immune defense and reproductive pace of life in Peromyscus mice. Ecology 88, 25162528.CrossRefGoogle ScholarPubMed
Matson, K. D., Ricklefs, R. E. and Klasing, K. C. (2005). A hemolysis-hemagglutination assay for characterizing constitutive innate humoral immunity in wild and domestic birds. Developmental and Comparative Immunology 29, 275286.CrossRefGoogle ScholarPubMed
Matzinger, P. (2002). The danger model: a renewed sense of self. Science 296, 301305.CrossRefGoogle Scholar
Mosmann, T. R., Cherwinski, H., Bond, M. W., Gieldin, M. A. and Coffman, R. L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology 136, 23482357.CrossRefGoogle ScholarPubMed
Nomura, F., Akashi, S., Sakao, Y., Sato, S., Kawal, T., Matsumoto, M., Nakanishi, K., Kimoto, M., Miyake, K., Takeda, K. and Akira, S. (2000). Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface Toll-like receptor 4 expression. Journal of Immunology 164, 34763479.CrossRefGoogle ScholarPubMed
Novoa, B., Romero, A., Mulero, V., Rodriguez, I., Fernandez, I. and Figueras, A. (2006). Zebrafish (Danio rerio) as a model for the study of vaccination against viral haemorrhagic septicemia virus (VHSV). Vaccine 24, 58065816.CrossRefGoogle Scholar
Paterson, S. and Lello, J. (2003). Mixed models: getting the best use of parasitological data. Trends in Parasitology 19, 370375.CrossRefGoogle ScholarPubMed
Pedersen, A. B. and Fenton, A. (2007). Emphasizing the ecology in parasite community ecology. Trends in Ecology and Evolution 22, 133139.CrossRefGoogle ScholarPubMed
Pinot de Moira, A., Fulford, A. J. C., Kabatereine, N. B., Kazibwe, F., Ouma, J. H., Dunne, D. W. and Booth, M. (2007). Microgeographical and tribal variations in water contact and Schistosoma mansoni exposure within a Ugandan fishing community. Tropical Medicine and International Health 12, 724735.CrossRefGoogle ScholarPubMed
Poulin, R. (1996). Richness, nestedness, and randomness in parasite infracommunity structure. Oecologia 105, 545551.CrossRefGoogle ScholarPubMed
Poulin, R. (2007). Are there general laws in parasite ecology Parasitology 134, 763776.CrossRefGoogle ScholarPubMed
Poulin, R. and Luque, J. L. (2003). A general test of the interactive-isolationist continuum in gastrointestinal parasite communities of fish. International Journal for Parasitology 33, 16231630.CrossRefGoogle ScholarPubMed
Ramsdell, F. (2003). Foxp3 and natural regulatory T cells: key to a cell lineage Immunity 19, 165168.CrossRefGoogle ScholarPubMed
Reiner, S. L. (2007). Development in motion: helper T cells at work. Cell 129, 3336.CrossRefGoogle ScholarPubMed
Roach, J. C., Glusman, G., Rowen, L., Kaur, A., Purcell, M. K., Smith, K. D., Hood, L. E. and Aderem, A. (2005). The evolution of vertebrate Toll-like receptors. Proceedings of the National Academy of Sciences, USA 102, 95779582.CrossRefGoogle ScholarPubMed
Roberts, M., Butterworth, A. E., Kimani, G., Kamau, T., Fulford, A. J., Dunne, D. W., Ouma, J. H. and Sturrock, R. F. (1993). Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection. Infection and Immunity 61, 49844993.CrossRefGoogle ScholarPubMed
Rohde, K., Worthen, W. B., Heap, M., Hugueny, B. and Guegan, J. F. (1998). Nestedness in assemblages of metazoan ecto- and endoparasites of marine fish. International Journal for Parasitology 28, 543549.CrossRefGoogle ScholarPubMed
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology 155, 11511164.CrossRefGoogle ScholarPubMed
Scott, P., Natovitz, P., Coffman, R. L., Pearce, E. and Sher, A. (1988). Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. Journal of Experimental Medicine 168, 16751684.CrossRefGoogle ScholarPubMed
Seth, R. B., Sun, L. and Chen, Z. J. (2006). Antiviral innate immunity pathways. Cell Research 16, 141147.CrossRefGoogle ScholarPubMed
Scharsack, J. P., Kalbe, M., Harrod, C. and Rauch, G. (2007). Habitat-specific adaptation of immune responses of stickleback (Gasterosteus aculeatus) lake and river ecotypes. Proceedings of the Royal Society B 274, 15231532.CrossRefGoogle ScholarPubMed
Stewart, G. R., Boussinesq, M., Coulson, T., Elson, L., Nutman, T. and Bradley, J. E. (1999). Onchocerciasis modulates the immune response to mycobacterial antigens. Clinical and Experimental Immunology 117, 517523.CrossRefGoogle ScholarPubMed
Stock, T. M. and Holmes, J. C. (1988). Functional relationships and microhabitat distributions of enteric helminths of grebes (Podicipedidae): the evidence for interactive communities. Journal of Parasitology 74, 214227.CrossRefGoogle ScholarPubMed
Sutmuller, R. P. M., Den Brok, M. H. M. G. M., Kramer, M., Bennink, E. J., Toonen, L. W. J., Kullberg, B.-J., Joosten, L. A., Akira, S., Netea, M. G. and Adema, G. J. (2006). Toll-like receptor 2 controls expansion and function of regulatory T cells. Journal of Clinical Investigation 116, 485494.CrossRefGoogle ScholarPubMed
Tamandl, D., Bahrami, M., Wessner, B., Weigel, G., Ploder, M., Furst, W., Roth, E., Boltz-Nitulescu, G. and Spittler, A. (2003). Modulation of toll-like receptor 4 expression on human monocytes by tumor necrosis factor and interleukin-6: tumor necrosis factor evokes lipopolysaccharide hyporesponsiveness, whereas interleukin-6 enhances lipopolysaccharide activity. Shock 20, 224229.CrossRefGoogle ScholarPubMed
Tchuem Tchuenté, L. A., Behnke, J. M., Gilbert, F. S., Southgate, V. R. and Vercruysse, J. (2003). Polyparasitism with Schistosoma haematobium and soil-transmitted helminth infections among school children in Loum, Cameroon. Tropical Medicine and International Health 8, 975986.CrossRefGoogle ScholarPubMed
Turner, J. D., Faulkner, H., Kamgno, J., Cormont, F., Van Snick, J., Else, K. J., Grencis, R. K., Behnke, J. M., Boussinesq, M. and Bradley, J. E. (2003). Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. Journal of Infectious Diseases 188, 17681775.CrossRefGoogle Scholar
Turner, J. D., Faulkner, H., Kamgno, J., Kennedy, M. W., Behnke, J., Boussinesq, M. and Bradley, J. E. (2005). Allergen-specific IgE and IgG4 are markers of resistance and susceptibility in a human intestinal nematode infection. Microbes and Infection 7, 990996.CrossRefGoogle Scholar
van Aubel, R. A., Keestra, A. M., Krooshoop, D. J., van Eden, W. and van Putten, J. P. (2007). Ligand-induced differential cross-regulation of Toll-like receptors 2, 4 and 5 in intestinal epithelial cells. Molecular Immunology 44, 37023714.CrossRefGoogle ScholarPubMed
Viney, M. E., Riley, E. M. and Buchanan, K. L. (2005). Optimal immune responses: immunocompetence revisited. Trends in Ecology and Evolution 20, 665669.CrossRefGoogle ScholarPubMed
Wakkach, A., Fournier, N., Brun, V., Breittmayer, J.-P., Cottrez, F. and Groux, H. (2003). Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605617.CrossRefGoogle Scholar
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M. and Murphy, K. M. (2006). Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24, 677688.CrossRefGoogle ScholarPubMed
Wegner, K. M., Kalbe, M. and Reusch, T. B. H. (2007). Innate versus adaptive immunity in sticklebacks: evidence for trade-offs from a selection experiment. Evolutionary Ecology 21, 473483.CrossRefGoogle Scholar
Willment, J. A. and Brown, G. D. (2008). C-type lectin receptors in antifungal immunity. Trends in Microbiology 16, 2732.CrossRefGoogle ScholarPubMed
Wilson, K. and Grenfell, B. T. (1997). Generalized linear modelling for parasitologists. Parasitology Today 13, 3338.CrossRefGoogle ScholarPubMed
Wilson, M. S., Taylor, M. D., Balic, A., Finney, C. A. M., Lamb, J. R. and Maizels, R. M. (2005). Suppression of allergic airway inflammation by helminth-induced regulatory T cells. Journal of Experimental Medicine 202, 11991212.CrossRefGoogle ScholarPubMed
Woodhams, D. C., Voyles, J., Lips, K. R., Carey, C. and Rollins-Smith, L. A. (2006). Predicted disease susceptibility in a Panamanian amphibian assemblage based on skin peptide defenses. Journal of Wildlife Diseases 42, 207218.CrossRefGoogle Scholar
Woolhouse, M. E. (1992). A theoretical framework for the immunoepidemiology of helminth infection. Parasite Immunology 14, 563578.CrossRefGoogle ScholarPubMed
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. and Fujita, T. (2004). The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nature Immunology 5, 730737.CrossRefGoogle ScholarPubMed
Zhou, L., Ivanov, I. I., Spolski, R., Min, R., Shenderov, K., Egawa, T., Levy, D. E., Leonard, W. J. and Littman, D. R. (2007). IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunology 8, 967974.CrossRefGoogle ScholarPubMed