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Infect. Immun. doi:10.1128/IAI.01644-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evaluation of the role of LcrV/TLR2-mediated immunomodulation in the virulence of Yersinia pestis

Department of Molecular Genetics and Microbiology; and Division of Infectious Diseases, Department of Medicine , University of Massachusetts Medical School, 55 Lake Avenue North, Worcester MA 01655

^* To whom correspondence should be addressed. Email: jon.goguen{at}umassmed.edu.

	Abstract

Pathogenic members of the Yersinia genus require the translocator protein, LcrV, for proper function of the type III secretion apparatus, which is crucial for virulence. LcrV has also been reported to play an independent immunosuppressive role via the induction of IL-10 through stimulation of Toll-like receptor 2 (TLR2). To investigate the LcrV-TLR2 interaction in vitro, recombinant His-tagged LcrV from Yersinia pestis was cloned and expressed in Escherichia coli and purified through Ni-NTA column chromatography. High concentrations (5µg/ml) of rLcrV stimulated TLR2 in vitro. Fractionation of rLcrV preparations via gel filtration reveals that only a minor component consisting of high molecular weight multimers or aggregates has TLR2 stimulating activity. Dimer and tetramer forms of rLcrV, which constitute the bulk of the material, do not have this activity. To investigate the potential role of LcrV/TLR2 in plague pathogenesis, we infected wild type and TLR2^-/- mice with virulent Y. pestis. No discernible difference between the two mouse strains in severity of disease or kinetics of survival after subcutaneous challenge was observed. IL-6, TNF, and IL-10 levels from spleen homogenates, bacterial load, and the extent of inflammation observed in organs from mice infected intravenously were also indistinguishable in both mouse strains. Taken together, our data indicate that the most abundant molecular species of Y. pestis LcrV do not efficiently activate TLR2-signaling, and that TLR2 mediated immunomodulation is unlikely to play a significant role in plague.

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