Marina A Freudenberg

Publications (130) View all

• Article: Mechanisms of chemical-induced innate immunity in allergic contact dermatitis.

  S F Martin, P R Esser, F C Weber, T Jakob, M A Freudenberg, M Schmidt, M Goebeler
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  ABSTRACT: Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long-lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical-specific, skin-homing CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti-infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.
  Allergy 05/2011; 66(9):1152-63. · 6.27 Impact Factor
• Article: Innate and adaptive immune responses in contact dermatitis: analogy with infections.

  M A Freudenberg, P R Esser, T Jakob, C Galanos, S F Martin
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  ABSTRACT: Allergic contact dermatitis (ACD) is an inflammatory skin disease of great and steadily increasing importance as an occupational health problem. The disease is induced by chemicals and metal ions which penetrate the skin and form complexes with host proteins. This process is accompanied by a strong, allergen-induced inflammatory reaction and leads to the migration of allergen-carrying dendritic cells (DC) from the skin to regional lymph nodes, where they promote generation of allergen-specific T cells. The latter are the ultimate effector cells of the disease. Re-exposure to the causative agent leads to the recruitment of the T effector cells, which then elicit the typical skin inflammatory reaction at the site of contact. Although DC and effector T cells play a protagonistic role in the sensitization and elicitation phase of ACD, respectively, other cell types including keratinocytes, NK cells, mast cells and B cells contribute to the pathogenesis of the disease. In this review the authors summarize recent findings that identify stress responses and innate immune pathways triggered by contact allergens and review recent data regarding the adaptive T cell response. The new data were collected mainly from studies on contact hypersensitivity (CHS), the corresponding experimental mouse model of human ACD. The elucidation of the molecular events involved in contact allergen-induced innate responses will help to design new treatment strategies and may allow to develop predictive in vitro assays for the identification of contact allergens.
  Giornale Italiano di Dermatologia e Venereologia 05/2009; 144(2):173-85.
• Source

  Available from: datafarm.de

  Article: Immunotherapy of patients with hormone-refractory prostate carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-peptide loaded dendritic cells--a pilot study.

  B Hildenbrand, B Sauer, O Kalis, C Stoll, M A Freudenberg, G Niedermann, J M Giesler, E Jüttner, J H Peters, B Häring, R Leo, C Unger, M Azemar
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  ABSTRACT: We conducted a pilot trial to assess the feasibility and tolerability of a prime/boost vaccine strategy using interferon-gamma (IFN-gamma) and autologous dendritic cells (DCs) pulsed with HLA-A2-specific prostate-specific antigen (PSA) peptides (PSA-1 [141-150]; PSA-2 [146-156]; PSA-3 [154-163]) for the treatment of 12 patients with hormone refractory prostate carcinoma. All patients were vaccinated four times with intracutaneously injected PSA-peptide loaded DCs after subcutaneous administration of IFN-gamma 2 hr before DC administration (50 microg/m(2) body surface). Objectives were safety, clinical benefit, clinical and biochemical response, quality of life, and immunological parameters. The vaccination was well tolerated without any vaccination-associated adverse events. One partial and one mixed responder were identified, four patients showed stable diseases. Two patients had a decrease and four a slow-down velocity slope in the PSA serum level. All responders showed a positive DTH-response, but only two a slight increase in PSA-peptide specific T-lymphocytes. The immunotherapy with IFN-gamma and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity.
  The Prostate 05/2007; 67(5):500-8. · 3.48 Impact Factor
• Article: Immunotherapy of patients with hormone‐refractory prostate carcinoma pre‐treated with interferon‐gamma and vaccinated with autologous PSA‐peptide loaded dendritic cells—A pilot study

  B. Hildenbrand, B. Sauer, O. Kalis, C. Stoll, M.A. Freudenberg, G. Niedermann, J.M. Giesler, E. Jüttner, J.H. Peters, B. Häring, R. Leo, C. Unger, M. Azemar
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  ABSTRACT: PURPOSEWe conducted a pilot trial to assess the feasibility and tolerability of a prime/boost vaccine strategy using interferon-gamma (IFN-γ) and autologous dendritic cells (DCs) pulsed with HLA-A2-specific prostate-specific antigen (PSA) peptides (PSA-1 [141–150]; PSA-2 [146–156]; PSA-3 [154–163]) for the treatment of 12 patients with hormone refractory prostate carcinoma.PATIENTS AND METHODS All patients were vaccinated four times with intracutaneously injected PSA-peptide loaded DCs after subcutaneous administration of IFN-γ 2 hr before DC administration (50 µg/m2 body surface). Objectives were safety, clinical benefit, clinical and biochemical response, quality of life, and immunological parameters.RESULTSThe vaccination was well tolerated without any vaccination-associated adverse events. One partial and one mixed responder were identified, four patients showed stable diseases. Two patients had a decrease and four a slow-down velocity slope in the PSA serum level. All responders showed a positive DTH-response, but only two a slight increase in PSA-peptide specific T-lymphocytes.CONCLUSION The immunotherapy with IFN-γ and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity. Prostate 67: 500–508, 2007. © 2007 Wiley-Liss, Inc.
  The Prostate 03/2007; 67(5):500 - 508. · 3.48 Impact Factor
• Source

  Available from: ncbi.nlm.nih.gov

  Article: Differences in innate defense mechanisms in endotoxemia and polymicrobial septic peritonitis.

  B Echtenacher, M A Freudenberg, R S Jack, D N Männel
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  ABSTRACT: Loss, reduction, or enhancement of the ability to respond to bacterial lipopolysaccharide (LPS) has no influence on survival of mice in a model of postoperative polymicrobial septic peritonitis induced by cecal ligation and puncture (CLP). This was demonstrated by using either mice with a defective Tlr4 gene, which encodes the critical receptor molecule for LPS responses, or mice deficient for LPS binding protein (LBP) or mice sensitized to LPS by Propionibacterium acnes. Though interleukin-12 (IL-12) and gamma interferon (IFN-gamma) play an important role in the sensitivity to LPS as well as in the resistance to several infections, loss of these cytokine pathways does not affect survival after CLP. Thus, neutralization of neither endogenous IL-12 nor IFN-gamma altered mortality. In addition, IFN-gamma receptor-deficient mice demonstrated the same sensitivity to CLP as mice with a functional IFN-gamma receptor. However, administration of IFN-gamma at the time of operation or pretreatment of both IFN-gamma-sensitive and IFN-gamma-resistant mice with IL-12 significantly enhanced mortality. This indicates that in the present infection model activation of innate defense mechanisms is not dependent on LPS recognition and does not require endogenous IL-12 or IFN-gamma function. Indeed, exogenous application of these two mediators had deleterious effects.
  Infection and Immunity 01/2002; 69(12):7271-6. · 4.16 Impact Factor