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J Med Microbiol 56 (2007), 459-465; DOI: 10.1099/jmm.0.46991-0
© 2007 Society for General Microbiology
ISSN 1473-5644

Toll-like receptor 2-mediated dendritic cell activation by a Porphyromonas gingivalis synthetic lipopeptide

Yasuyuki Asai, Yutaka Makimura and Tomohiko Ogawa

Department of Oral Microbiology, Asahi University School of Dentistry, Gifu 501-0296, Japan

Correspondence
Tomohiko Ogawa
tomo527{at}dent.asahi-u.ac.jp

Received 7 October 2006
Accepted 21 November 2006

A PG1828 gene-encoded triacylated lipoprotein was previously isolated from a Porphyromonas gingivalis lipopolysaccharide preparation as a Toll-like receptor (TLR) 2 agonist and its lipopeptide derivatives were synthesized based on the chemical structure. In the present study, granulocyte–macrophage colony stimulating factor-differentiated bone marrow-derived dendritic cells (BMDDCs) were stimulated separately with the P. gingivalis synthetic lipopeptide N-palmitoyl-S-[2-pentadecanoyloxy, 3-palmitoyloxy-(2R)-propyl]-L-Cys-Asn-Ser-Gln-Ala-Lys (PGTP2-RL) and its glyceryl stereoisomer (PGTP2-SL). Only PGTP2-RL activated BMDDCs from wild-type mice to secrete tumour necrosis factor-{alpha}, interleukin (IL)-6, IL-10 and IL-12p40, whilst PGTP2-RL-induced cytokine production was eliminated in TLR2 knockout (–/–) BMDDCs. BMDDCs from wild-type mice but not TLR2–/– mice responded to PGTP2-RL as well as Pam3CSK4 by increasing the expression of maturation markers, including CD80 (B7-1), CD86 (B7-2), CD40, CD275 (B7RP-1/inducible T-cell co-stimulatory ligand) and major histocompatibility complex class II. Taken together, these results indicate that the fatty acid residue at the glycerol position in the P. gingivalis lipopeptide plays a pivotal role in TLR2-mediated dendritic cell activation.

Abbreviations: BMC, bone marrow cell; BMDDC, bone marrow-derived dendritic cell; DC, dendritic cell; ICOSL, inducible T-cell co-stimulatory ligand; IL, interleukin; MHC, major histocompatibility complex; PE, phycoerythrin; rmGM-CSF, recombinant mouse granulocyte–macrophage colony stimulating factor; Th, T-helper type; TLR, Toll-like receptor; TNF, tumour necrosis factor.




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