Journal article
Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling
L Tribolet, C Cantacessi, DA Pickering, S Navarro, DL Doolan, A Trieu, H Fei, Y Chao, A Hofmann, RB Gasser, PR Giacomin, A Loukas
Journal of Infectious Diseases | Published : 2015
Abstract
Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation of its crystal structure and studies addressing its immunobiology, the function of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and downregulated the transcription of approximately 1000 B-cell messenger RNAs (mRNAs), while only approximately 100 mRNAs were upregulated, compared with control-treated cells. The expression of a range of molecules was affected by Na-ASP-2, including factors involved in leukocyte transendothelial migration p..
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Funding Acknowledgements
This work was supported by the Australian Research Council (Linkage Project grant 100100092 to R. B. G., A. H., and A. L.); the National Health and Medical Research Council (NHMRC; Program Grant 1037304 to A. L. and D. L. D.; NHMRC Overseas Biomedical Fellowship 613718 to P. G.; NHMRC Early Career Research Fellowship 1052936 to C. C.; and NHMRC Principal Research Fellowships 1020114 to A. L. and 1023636 to D. L. D.); the Victoria Life Sciences Computation Initiative (VLSCI VR0007 to R. B. G.) on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government; and an Australian Postgraduate Award from James Cook University (to L. T.).