Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2

C. J. Hertz, S. M. Kiertscher, P. J. Godowski, D. A. Bouis, M. V. Norgard, M. D. Roth, R. L. Modlin

Research output: Contribution to journalArticle

300 Citations (Scopus)

Abstract

The ability of dendritic cells (DC) to initiate immune responses in naive T cells is dependent upon a maturation process that allows the cells to develop their potent Ag-presenting capacity. Although immature DC can be derived in vitro by treatment of peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided by TNF-α, CD40 ligand, or LPS are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC through Toll-like receptor (TLR) 2, we also investigated whether lipoproteins can drive DC maturation. Immature DC were cultured with or without lipoproteins and were monitored for expression of cell surface markers indicative of maturation. Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression and endocytic activity; these lipopeptide-matured DC also displayed enhanced T cell stimulatory capacity in MLR, as measured by T cell proliferation and IFN-γ secretion. The lipid moiety of the lipopeptide was found to be essential for induction of maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before addition of lipopeptide blocked the phenotypic and functional changes associated with DC maturation. These results demonstrate that lipopeptides can stimulate DC maturation via TLR2, providing a mechanism by which products of bacteria can participate in the initiation of an immune response.

Original languageEnglish (US)
Pages (from-to)2444-2450
Number of pages7
JournalJournal of Immunology
Volume166
Issue number4
StatePublished - Feb 15 2001

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Lipopeptides
Toll-Like Receptor 2
Dendritic Cells
Lipoproteins
T-Lymphocytes
Monocytes
CD40 Ligand
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Cell Proliferation
Bacteria
Lipids

ASJC Scopus subject areas

  • Immunology

Cite this

Hertz, C. J., Kiertscher, S. M., Godowski, P. J., Bouis, D. A., Norgard, M. V., Roth, M. D., & Modlin, R. L. (2001). Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. Journal of Immunology, 166(4), 2444-2450.

Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. / Hertz, C. J.; Kiertscher, S. M.; Godowski, P. J.; Bouis, D. A.; Norgard, M. V.; Roth, M. D.; Modlin, R. L.

In: Journal of Immunology, Vol. 166, No. 4, 15.02.2001, p. 2444-2450.

Research output: Contribution to journalArticle

Hertz, CJ, Kiertscher, SM, Godowski, PJ, Bouis, DA, Norgard, MV, Roth, MD & Modlin, RL 2001, 'Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2', Journal of Immunology, vol. 166, no. 4, pp. 2444-2450.
Hertz CJ, Kiertscher SM, Godowski PJ, Bouis DA, Norgard MV, Roth MD et al. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. Journal of Immunology. 2001 Feb 15;166(4):2444-2450.
Hertz, C. J. ; Kiertscher, S. M. ; Godowski, P. J. ; Bouis, D. A. ; Norgard, M. V. ; Roth, M. D. ; Modlin, R. L. / Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. In: Journal of Immunology. 2001 ; Vol. 166, No. 4. pp. 2444-2450.
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