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Infection and Immunity, June 2007, p. 3033-3042, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01549-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of D-Alanylation of Streptococcus gordonii Lipoteichoic Acid in Innate and Adaptive Immunity{triangledown}

Karenn G. Chan,2 Matt Mayer,2 Elisabeth M. Davis,2 Scott A. Halperin,2,3,4 Tong-Jun Lin,2,3,4 and Song F. Lee1,2,3,4*

Department of Applied Oral Sciences, Faculty of Dentistry,1 Departments of Microbiology and Immunology and Pediatrics,2 Faculty of Medicine, Dalhousie University, and IWK Health Centre,3 Halifax, Nova Scotia B3H 3J5, Canada4

Received 26 September 2006/ Returned for modification 22 November 2006/ Accepted 22 March 2007

In recent years, there has been considerable interest in using the oral commensal gram-positive bacterium Streptococcus gordonii as a live vaccine vector. The present study investigated the role of D-alanylation of lipoteichoic acid (LTA) in the interaction of S. gordonii with the host innate and adaptive immune responses. A mutant strain defective in D-alanylation was generated by inactivation of the dltA gene in a recombinant strain of S. gordonii (PM14) expressing a fragment of the S1 subunit of pertussis toxin. The mutant strain was found to be more susceptible to killing by polymyxin B, nisin, magainin II, and human β defensins than the parent strain. When it was examined for binding to murine bone marrow-derived dendritic cells (DCs), the dltA mutant exhibited 200- to 400-fold less binding than the parent but similar levels of binding were shown for Toll-like receptor 2 (TLR2) knockout DCs and HEp-2 cells. In a mouse oral colonization study, the mutant showed a colonization ability similar to that of the parent and was not able to induce a significant immune response. The mutant induced significantly less interleukin 12p70 (IL-12p70) and IL-10 than the parent from DCs. LTA purified from the bacteria induced tumor necrosis factor-alpha and IL-6 production from wild-type DCs but not from TLR2 knockout DCs, and the mutant LTA induced a significantly smaller amount of these two cytokines. These results show that D-alanylation of LTA in S. gordonii plays a role in the interaction with the host immune system by contributing to the relative resistance to host defense peptides and by modulating cytokine production by DCs.


* Corresponding author. Mailing address: Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada. Phone: (902) 494-8799. Fax: (902) 494-6621. E-mail: song.lee{at}dal.ca

{triangledown} Published ahead of print on 9 April 2007.

Editor: J. N. Weiser


Infection and Immunity, June 2007, p. 3033-3042, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01549-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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