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Probing of a Human Proteome Microarray With a Recombinant Pathogen Protein Reveals a Novel Mechanism by Which Hookworms Suppress B-cell Receptor Signaling

Probing of a Human Proteome Microarray With a Recombinant Pathogen Protein Reveals a Novel Mechanism by Which Hookworms Suppress B-cell Receptor Signaling

Leon Tribolet, Cinzia Cantacessi, Darren A Pickering, Severine Navarro, Denise L Doolan, Angela Trieu, Huang Fei, Yang Chao, Andreas Hofmann, Robin B Gasser, Paul R Giacomin, Alex Loukas

J Infect Dis. 2015 Feb 1;211(3):416-25.

PMID: 25139017

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 pathways and the B-cell signaling receptor pathway. Of note was the downregulated transcription of lyn and pi3k, molecules that are known to interact with CD79A and control B-cell receptor signaling processes. Together, these results highlight a previously unknown interaction between a hookworm-secreted protein and B cells, which has implications for helminth-driven immunomodulation and vaccine development. Further, the novel use of human protein microarrays to identify host-pathogen interactions, coupled with ex vivo binding studies and subsequent analyses of global gene expression in human host cells, demonstrates a new pipeline by which to explore the molecular basis of infectious diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248697	LYN A human			Price

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