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Infection and Immunity, August 2005, p. 5015-5021, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5015-5021.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Endocarditis-Associated Oral Streptococci Promote Rapid Differentiation of Monocytes into Mature Dendritic Cells

Chin-Lo Hahn,^* Harvey A. Schenkein, and John G. Tew

Clinical Research Center for Periodontal Disease, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia

Received 18 October 2004/ Returned for modification 27 December 2004/ Accepted 28 March 2005

Endocarditis is frequently attributable to oral streptococci, but mechanisms of pathogenesis are not well understood, although monocytes appear to be important. High titers of interleukin-12 (IL-12) are produced by peripheral blood mononuclear cells (PBMC) after engaging Streptococcus mutans, but monocytes in developing endocardial vegetations tend to disappear rather than become macrophages. These data prompted the hypothesis that streptococcus-infected monocytes differentiate into short-lived IL-12-producing dendritic cells (DCs) rather than macrophages. PBMC from healthy subjects were stimulated with six isolates of oral streptococci, three nonstreptococcal oral bacteria, or IL-4 plus granulocyte-macrophage colony-stimulating factor, and the appearance of cells with markers typical of mature DCs (CD83⁺, CD86⁺, CD11c⁺, and CD14^–) was monitored. Supernatant fluids from the PBMC cultures were harvested and IL-12 p70 levels were determined. S. mutans-stimulated monocytes were analyzed for their ability to elicit allogeneic mixed-lymphocyte reactions. All streptococci examined, except one strain of Streptococcus oralis (35037), rapidly induced up-regulation of CD83 and CD86 and a loss of CD14 in the CD11c⁺ monocyte population within 20 h. Induction of IL-12 was CD14 dependent and correlated with streptococcal isolates that promoted the DC phenotype. Major histocompatibility complex (MHC) class II expression was up-regulated by S. mutans, and these cells were short-lived and elicited potent allogeneic mixed-lymphocyte reactions typical of DCs. In summary, monocytes stimulated with endocarditis-associated oral streptococci rapidly exhibited the DC phenotype and functions. These data suggest that the initiation of bacterial endocarditis by oral streptococci may involve monocyte-to-DC differentiation, and this may help explain the low levels of macrophages in the site.

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* Corresponding author. Mailing address: Department of Endodontics, School of Dentistry, Lyons Building, Rm. 322, 520 N. 12th Street, P.O. Box 980566, Richmond, VA 23298-0566. Phone: (804) 828-0784. Fax: (804) 828-4913. E-mail: chahn{at}hsc.vcu.edu.

Editor: J. D. Clements

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Infection and Immunity, August 2005, p. 5015-5021, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5015-5021.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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