Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-26T07:15:30.725Z Has data issue: false hasContentIssue false
  • English
  • Français

Increased exposure to Plasmodium chabaudi antigens sustains cross-reactivity and avidity of antibodies binding Nippostrongylus brasiliensis: dissecting cross-phylum cross-reactivity in a rodent model

Published online by Cambridge University Press:  22 October 2015

KAREN J. FAIRLIE-CLARKE ,
CHRISTINA HANSEN ,
JUDITH E. ALLEN  and
ANDREA L. GRAHAM
KAREN J. FAIRLIE-CLARKE*
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh, UK
CHRISTINA HANSEN
Affiliation:
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA
JUDITH E. ALLEN
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh, UK
ANDREA L. GRAHAM
Affiliation:
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh, UK Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA
*
*Corresponding author: Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh, UK. E-mail: Karen.Fairlie-Clarke@glasgow.ac.uk
Get access Rights & Permissions [Opens in a new window]

Summary

Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)–Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-119. The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.

Keywords

antibodyaviditycross-reactivityparasite doseco-infectionmalarianematodeantigen exposure
Type
Research Article
Information
Parasitology , Volume 142 , Issue 14 , December 2015 , pp. 1703 - 1714
Check for updates
Copyright
Copyright © Cambridge University Press 2015 

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

Acevedo, N. and Caraballo, L. (2011). IgE cross-reactivity between Ascaris lumbricoides and mite allergens: possible influences on allergic sensitization and asthma. Parasite Immunology 33, 309–321.Google Scholar
Achtman, A. H., Khan, M., Maclennan, I. C. and Langhorne, J. (2003). Plasmodium chabaudi chabaudi infection in mice induces strong B cell responses and striking but temporary changes in splenic cell distribution. Journal of Immunology 171, 317–324.Google Scholar
Achtman, A. H., Stephens, R., Cadman, E. T., Harrison, V. and Langhorne, J. (2007). Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi . Parasite Immunology 29, 435–444.Google Scholar
Beale, G. H., Carter, R. and Walliker, D. (1978). Genetics. In Rodent Malaria (eds. Killick-Kendrick, R. and Peters, W.), 213–244. Academic Press, London.Google Scholar
Bergmann-Leitner, E. S., Duncan, E. H. and Angov, E. (2009). MSP-1p42-specific antibodies impact growth and development of intra-erythrocytic parasites of Plasmodium falciparum . Malaria Journal 8, 183.Google Scholar
Bjorkman, C., Naslund, K., Stenlund, S., Maley, S. W., Buxton, D. and Uggla, A. (1999). An IgG avidity ELISA to discriminate between recent and chronic Neospora caninum infection. Journal of Veterinary Diagnostic Investigation 11, 41–44.CrossRefGoogle ScholarPubMed
Casadevall, A. and Pirofski, L. A. (2007). Antibody-mediated protection through cross-reactivity introduces a fungal heresy into immunological dogma. Infection and Immunity 75, 5074–5078.CrossRefGoogle ScholarPubMed
Castillo-Mendez, S. I., Zago, C. A., Sardinha, L. R., Freitas Do Rosario, A. P., Alvarez, J. M. and D'imperio Lima, M. R. (2007). Characterization of the spleen B-cell compartment at the early and late blood-stage Plasmodium chabaudi malaria. Scandinavian Journal of Immunology 66, 309–319.Google Scholar
Chaplin, D. D. (2010). Overview of the immune response. Journal of Allergy and Clinical Immunology 125, S3–23.Google Scholar
Chan, T. D. and Brink, R. (2012). Affinity-based selection and the germinal center response. Immunological Reviews 247, 11–23.Google Scholar
Cox, F. E. (2001). Concomitant infections, parasites and immune responses. Parasitology 122 Suppl, S23–38.Google Scholar
D'imperio Lima, M. R., Alvarez, J. M., Furtado, G. C., Kipnis, T. L., Coutinho, A. and Minoprio, P. (1996). Ig-isotype patterns of primary and secondary B cell responses to Plasmodium chabaudi chabaudi correlate with IFN-gamma and IL-4 cytokine production with CD45RB expression by CD4+ spleen cells. Scandinavian Journal of Immunology 43, 263–270.Google Scholar
Diaz-Saez, V., Merino-Espinosa, G., Morales-Yuste, M., Corpas-Lopez, V., Pratlong, F., Morillas-Marquez, F. and Martin-Sanchez, J. (2014). High rates of Leishmania infantum and Trypanosoma nabiasi infection in wild rabbits (Oryctolagus cuniculus) in sympatric and syntrophic conditions in an endemic canine leishmaniasis area: epidemiological consequences. Veterinary Parasitology 202, 119–127.Google Scholar
Douglas, A. D., Williams, A. R., Knuepfer, E., Illingworth, J. J., Furze, J. M., Crosnier, C., Choudhary, P., Bustamante, L. Y., Zakutansky, S. E., Awuah, D. K., Alanine, D. G., Theron, M., Worth, A., Shimkets, R., Rayner, J. C., Holder, A. A., Wright, G. J. and Draper, S. J. (2014). Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. Journal of Immunology 192, 245–258.Google Scholar
Eisen, H. N. and Chakraborty, A. K. (2010). Evolving concepts of specificity in immune reactions. Proceedings of the National Academy of Sciences of the United States of America 107, 22373–22380.Google Scholar
Fairlie-Clarke, K. J., Shuker, D. M. and Graham, A. L. (2009). “Why do adaptive immune responses cross-react?”. Evolutionary Applications 2, 122–131.Google Scholar
Fairlie-Clarke, K. J., Lamb, T. J., Langhorne, J., Graham, A. L. and Allen, J. E. (2010). Antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity. BMC Immunology 11, 6.Google Scholar
Gonzalez-Fernandez, A. and Milstein, C. (1998). Low antigen dose favours selection of somatic mutants with hallmarks of antibody affinity maturation. Immunology 93, 149–153.Google Scholar
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. The Journal of Infectious Diseases 191, 410–421.CrossRefGoogle ScholarPubMed
Gurish, M. F., Bryce, P. J., Tao, H., Kisselgof, A. B., Thornton, E. M., Miller, H. R., Friend, D. S. and Oettgen, H. C. (2004). IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis . Journal of Immunology 172, 1139–1145.Google Scholar
Hensmann, M., Li, C., Moss, C., Lindo, V., Greer, F., Watts, C., Ogun, S. A., Holder, A. A. and Langhorne, J. (2004). Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response. European Journal of Immunology 34, 639–648.Google Scholar
Hill, D. L., Eriksson, E. M., Li Wai Suen, C. S., Chiu, C. Y., Ryg-Cornejo, V., Robinson, L. J., Siba, P. M., Mueller, I., Hansen, D. S. and Schofield, L. (2013). Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria. PLoS ONE 8, e74627.Google Scholar
Hoeve, M. A., Mylonas, K. J., Fairlie-Clarke, K. J., Mahajan, S. M., Allen, J. E. and Graham, A. L. (2009). Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice. BMC Immunology 10, 60.Google Scholar
Lima, M. R. D., Bandeira, A., Falanga, P., Freitas, A. A., Kipnis, T. L., Dasilva, L. P. and Coutinho, A. (1991). Clonal analysis of lymphocyte-B responses to Plasmodium-chabaudi infection of normal and immunoprotected mice. International Immunology 3, 1207–1216.Google Scholar
Lima, M. R. D., Alvarez, J. M., Furtado, G. C., Kipnis, T. L., Coutinho, A. and Minoprio, P. (1996). Ig-isotype patterns of primary and secondary B cell responses to Plasmodium chabaudi chabaudi correlate with IFN-gamma and IL-4 cytokine production and with CD45RB expression by CD4(+) spleen cells. Scandinavian Journal of Immunology 43, 263–270.CrossRefGoogle Scholar
Mota, M. M., Brown, K. N., Do Rosario, V. E., Holder, A. A. and Jarra, W. (2001). Antibody recognition of rodent malaria parasite antigens exposed at the infected erythrocyte surface: specificity of immunity generated in hyperimmune mice. Infection and Immunity 69, 2535–2541.Google Scholar
Naus, C. W., Jones, F. M., Satti, M. Z., Joseph, S., Riley, E. M., Kimani, G., Mwatha, J. K., Kariuki, C. H., Ouma, J. H., Kabatereine, N. B., Vennervald, B. J. and Dunne, D. W. (2003). Serological responses among individuals in areas where both schistosomiasis and malaria are endemic: cross-reactivity between Schistosoma mansoni and Plasmodium falciparum . The Journal of Infectious Diseases 187, 1272–1282.CrossRefGoogle ScholarPubMed
Nguyen, H. H., Zemlin, M., Ivanov, Ii., Andrasi, J., Zemlin, C., Vu, H. L., Schelonka, R., Schroeder, H. W. Jr. and Mestecky, J. (2007). Heterosubtypic immunity to influenza A virus infection requires a properly diversified antibody repertoire. Journal of Virology 81, 9331–9338.Google Scholar
Nieuwenhuizen, N. E., Meter, J. M., Horsnell, W. G., Hoving, J. C., Fick, L., Sharp, M. F., Darby, M. G., Parihar, S. P., Brombacher, F. and Lopata, A. L. (2013). A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis . Plos Neglected Tropical Diseases 7, e2395.Google Scholar
Pancer, Z. and Cooper, M. D. (2006). The evolution of adaptive immunity. Annual Review of Immunology 24, 497–518.Google Scholar
Pedersen, A. B. and Fenton, A. (2007). Emphasizing the ecology in parasite community ecology. Trends in Ecology and Evolution 22, 133–139.Google Scholar
Petney, T. N. and Andrews, R. H. (1998). Multiparasite communities in animals and humans: frequency, structure and pathogenic significance. International Journal of Parasitology 28, 377–393.Google Scholar
Pierrot, C., Wilson, S., Lallet, H., Lafitte, S., Jones, F. M., Daher, W., Capron, M., Dunne, D. W. and Khalife, J. (2006). Identification of a novel antigen of Schistosoma mansoni shared with Plasmodium falciparum and evaluation of different cross-reactive antibody subclasses induced by human schistosomiasis and malaria. Infection and Immunity 74, 3347–3354.Google Scholar
Rieck, M., Arechiga, A., Onengut-Gumuscu, S., Greenbaum, C., Concannon, P. and Buckner, J. H. (2007). Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. Journal of Immunology 179, 4704–4710.Google Scholar
Sotillo, J., Sanchez-Flores, A., Cantacessi, C., Harcus, Y., Pickering, D., Bouchery, T., Camberis, M., Tang, S. C., Giacomin, P., Mulvenna, J., Mitreva, M., Berriman, M., Legros, G., Maizels, R. M. and Loukas, A. (2014). Secreted proteomes of different developmental stages of the gastrointestinal nematode Nippostrongylus brasiliensis . Molecular and Cell Proteomics 13, 2736–2751 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.Google Scholar
Tarlinton, D. M. and Smith, K. G. (2000). Dissecting affinity maturation: a model explaining selection of antibody-forming cells and memory B cells in the germinal centre. Immunology Today 21, 436–441.Google Scholar
Timms, R., Colegrave, N., Chan, B. H. and Read, A. F. (2001). The effect of parasite dose on disease severity in the rodent malaria Plasmodium chabaudi . Parasitology 123, 1–11.Google Scholar
Toellner, K. M., Jenkinson, W. E., Taylor, D. R., Khan, M., Sze, D. M., Sansom, D. M., Vinuesa, C. G. and Maclennan, I. C. (2002). Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. Journal of Experimental Medicine 195, 383–389.Google Scholar
Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature 302, 575–581.CrossRefGoogle ScholarPubMed
Van Remoortere, A., Bank, C. M., Nyame, A. K., Cummings, R. D., Deelder, A. M. and Van Die, I. (2003). Schistosoma mansoni-infected mice produce antibodies that cross-react with plant, insect, and mammalian glycoproteins and recognize the truncated biantennaryN-glycan Man3GlcNAc2-R. Glycobiology 13, 217–225.CrossRefGoogle ScholarPubMed
Wang, F., Sen, S., Zhang, Y., Ahmad, I., Zhu, X., Wilson, I. A., Smider, V. V., Magliery, T. J. and Schultz, P. G. (2013). Somatic hypermutation maintains antibody thermodynamic stability during affinity maturation. Proceedings of the National Academy of Sciences of the United States of America 110, 4261–4266.Google Scholar
Wang, Y., Huang, G., Wang, J., Molina, H., Chaplin, D. D. and Fu, Y. X. (2000). Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin. European Journal of Immunology 30, 2226–2234.Google Scholar
Weidanz, W. P., Batchelder, J. M., Flaherty, P., Lafleur, G., Wong, C. and Van der Heyde, H. C. (2005). Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria. Experimental Parasitology 111, 97–104.Google Scholar
Xu, B. X. and Powell, M. R. (1991). Carbohydrate epitopes are responsible for antibody cross-reactivity in Trypanosoma cruzi-infected mice. Journal of Parasitology 77, 808–810.Google Scholar
Yasodhara, P., Ramalakshmi, B. A. and Sarma, M. K. (2001). A new approach to differentiate recent vs chronic Toxoplasma infection: avidity ELISA in Toxoplasma serology. Indian Journal of Medical Microbiology 19, 145–148.Google Scholar
Yin, J., Beuscher, A. E. T., Andryski, S. E., Stevens, R. C. and Schultz, P. G. (2003). Structural plasticity and the evolution of antibody affinity and specificity. Journal of Molecular Biology 330, 651–656.Google Scholar
Supplementary material: File

Fairlie-Clarke supplementary material

Figure S1

Download Fairlie-Clarke supplementary material(File)
File 634.4 KB