Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Infect Dis. 2015 Feb 1;211(3):416-25. doi: 10.1093/infdis/jiu451. Epub 2014 Aug 19.

Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling.

Author information

1
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns.
2
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns Department of Veterinary Medicine, University of Cambridge, United Kingdom.
3
QIMR Berghofer Medical Research Institute.
4
BGI-Shenzhen, China.
5
Eskitis Institute, Griffith University, Brisbane.
6
Faculty of Veterinary Science, University of Melbourne, Australia.

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.

KEYWORDS:

B cell; CD79A; Na-ASP-2; Necator americanus; SCP/TAPS; antigen receptor; hookworm; host–pathogen interaction; protein microarray

PMID:
25139017
DOI:
10.1093/infdis/jiu451
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center