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Infection and Immunity, September 2003, p. 5169-5177, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5169-5177.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Insertional Inactivation of pac and rmlB Genes Reduces the Release of Tumor Necrosis Factor Alpha, Interleukin-6, and Interleukin-8 Induced by Streptococcus mutans in Monocytic, Dental Pulp, and Periodontal Ligament Cells

Marc Engels-Deutsch,1 Annelise Pini,1 Yoshihisa Yamashita,2 Yukie Shibata,2 Youssef Haikel,3 Marie Schöller-Guinard,1 and Jean-Paul Klein1*

INSERM U 392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch,1 INSERM U 595, Université Louis Pasteur de Strasbourg, F-67085 Strasbourg Cedex, France,3 Department of Preventive Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan2

Received 7 March 2003/ Returned for modification 16 April 2003/ Accepted 28 May 2003

Streptococcus mutans possesses different cell wall molecules, such as protein of the I/II family, the serotype f polysaccharide rhamnose glucose polymer (RGP), and lipoteichoic acid (LTA), which act as adhesins and modulins, allowing S. mutans to colonize teeth and cause dental caries and pulpitis. We tested several isogenic mutants of S. mutans defective in protein I/II and/or RGP, as well as purified modulins such as protein I/II, RGP, and LTA, for their binding and activation abilities on monocytic, dental pulp (DP), and periodontal ligament (PDL) cells. Our results demonstrate that both protein I/II and RGP play important roles in streptococcal adherence to human monocytic and fibroblastic cells, whereas LTA is only a minor adhesin. In the activation process, the cytokine response elicited is polarized toward a Th1 response which seems principally due to protein I/II and RGP. Even if protein I/II seems to be more efficient in its purified form in triggering cells to release interleukin-8 (IL-8), RGP is the most efficient cytokine-stimulating component in intact bacteria, while LTA plays only a minor role. In cell activation, we showed, by using either cytochalasin D or coated ligands, that internalization of either S. mutans, S. mutans isogenic mutants, or purified ligands is not necessary to trigger cells to release IL-8. We also showed that, besides the implication of monocytes in pulpal inflammation, fibroblast-like cells such as DP and PDL cells are also actively implicated in local inflammation and in the generation of a Th1 response after stimulation with S. mutans cells or antigens.

* Corresponding author. Mailing address: INSERM U 392, Faculté de Pharmacie, 74 route du Rhin, F-67400 Illkirch, France. Phone: 33 3 90 24 41 84. Fax: 33 3 90 24 43 08. E-mail: jpklein{at}pharma.u-strasbg.fr.

Editor: J. N. Weiser

Infection and Immunity, September 2003, p. 5169-5177, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5169-5177.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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