Authors: Weigt H.¹; Mühlradt P.F.²; Emmendörffer A.³; Krug N.¹; Braun A.¹

Source: Immunobiology, Volume 207, Number 3, 1 May 2003 , pp. 223-233(11)

Publisher: Urban & Fischer

Abstract:

Dendritic cells (DC) modulate immune responses depending on the nature of the antigens. Receptors capable of discriminating these antigens on the basis of the pathogen-associated molecular patterns (PAMP) belong to the Toll-like receptor (TLR) family. The macrophage-activating lipopeptide 2 kDa (MALP-2), a synthetic lipopeptide derived from Mycoplasma fermentans, signals through TLR-2 and TLR-6. The aim of this study was to examine whether MALP-2 can modulate the functional properties of human monocyte-derived DC. The effects of this treatment were compared to those of the TLR-4 agonist lipopolysaccharide (LPS). To ensure clinical applicability, DC were generated under serum-free conditions. MALP-2 and LPS stimulation induced the expression of CD83 and increased the expressions of CD80, CD86, HLA-ABC and CD40. Furthermore, both substances decreased the endocytotic capacity of DC and induced the release of bioactive TNF- and IL-10, whereas LPS additionally increased IL-12 release. Pretreatment with both substances boosted the allostimulatory capacity of DC. In a coculture with autologous lymphocytes, either MALP-2 or LPS pretreated DC induced a marked proliferation of lymphocytes, but only DC prestimulated with MALP-2 activated lymphocytes to produce the cytokines IL-4, IL-5 and IFN-. No polarisation of lymphocytes into T-helper (Th)1 or Th2 was detected. These data indicate that MALP-2 is a potential candidate to modulate DC for clinical applications.

Document Type: Research article

DOI: http://dx.doi.org/10.1078/0171-2985-00234

Affiliations: 1: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany 2: Wound Healing Research Group, Gruenderzentrum, Braunschweig, Germany 3: MODEX Therapeutics GmbH Leipzig, Germany

Publication date: 2003-05-01

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