This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brännström, K.
Right arrow Articles by Gullberg, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brännström, K.
Right arrow Articles by Gullberg, M.

 Previous Article  |  Next Article 

Infection and Immunity, March 2009, p. 1144-1154, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01126-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Schistosoma mansoni Protein Sm16/SmSLP/SmSPO-1 Assembles into a Nine-Subunit Oligomer with Potential To Inhibit Toll-Like Receptor Signaling{triangledown}

Kristoffer Brännström,1 Mikael E. Sellin,1 Per Holmfeldt,1 Maria Brattsand,2 and Martin Gullberg1*

Departments of Molecular Biology,1 Public Health and Clinical Medicine, Umeå University, Umeå, Sweden2

Received 9 September 2008/ Returned for modification 22 October 2008/ Accepted 27 December 2008

The Sm16/SmSLP/SmSPO-1 (Sm16) protein is secreted by the parasite Schistosoma mansoni during skin penetration and has been ascribed immunosuppressive activities. Here we describe the strategy behind the design of a modified Sm16 protein with a decreased aggregation propensity, thus facilitating the expression and purification of an Sm16 protein that is soluble in physiological buffers. The Stokes radii and sedimentation coefficients of recombinant and native proteins indicate that Sm16 is an approximately nine-subunit oligomer. Analysis of truncated Sm16 derivatives showed that both oligomerization and binding to the plasma membrane of human cells depend on multiple C-terminal regions. For analysis of immunomodulatory activities, Sm16 was expressed in Pichia pastoris to facilitate the preparation of a pyrogen/endotoxin-free purified protein. Recombinant Sm16 was found to have no effect on T-lymphocyte activation, cell proliferation, or the basal level of cytokine production by whole human blood or monocytic cells. However, Sm16 exerts potent inhibition of the cytokine response to the Toll-like receptor (TLR) ligands lipopolysaccharide (LPS) and poly(I:C) while being less efficient at inhibiting the response to the TLR ligand peptidoglycan or a synthetic lipopeptide. Since Sm16 specifically inhibits the degradation of the IRAK1 signaling protein in LPS-stimulated monocytes, our findings indicate that inhibition is exerted proximal to the TLR complex.

* Corresponding author. Mailing address: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden. Phone: 46 90 7852532. Fax: 46 90 772630. E-mail: martin.gullberg{at}molbiol.umu.se

{triangledown} Published ahead of print on 5 January 2009.

Editor: J. F. Urban, Jr.

Infection and Immunity, March 2009, p. 1144-1154, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01126-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»