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Infect. Immun. doi:10.1128/IAI.01549-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Role of D-alanylation of Streptococcus gordonii Lipoteichoic Acid in Innate and Adaptive Immunity

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

^* To whom correspondence should be addressed. Email: song.lee{at}dal.ca.

	Abstract

In recent years, there has been considerable interest in using the oral commensal Gram-positive bacterium Streptococcus gordonii as a live vaccine vector. This study investigated the role of D-alanylation of LTA in the interaction of S. gordonii with the host innate and adaptive immune response. A mutant defective in D-alanylation was generated by inactivation of the dltA gene in a recombinant strain of S. gordonii (PM14) expressing the a fragment of the S1 subunit of pertussis toxin. The mutant strain was found to be more susceptible to killing by polymixin B, nisin, magainin II, and human defensins than the parent strain. When 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 to toll-like receptor 2 (TLR2) knockout DCs and HEp-2 cells. In a mouse oral colonization study, the mutant showed similar colonization ability as the parent and was not able to induce a significant immune response. The mutant induced significantly less IL-12p70 and IL-10 than the parent from DCs. LTA purified from the bacteria induced TNF- and IL-6 production from wild-type DCs, but not from TLR2 knockout DCs, with the mutant LTA induced significantly less 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 relative resistance to host defense peptides and modulation of cytokine production by DCs.

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