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Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4.

التفاصيل البيبلوغرافية
العنوان: Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4.
المؤلفون: Marcelo Hill, Ala-Eddine Deghmane, Mercedes Segovia, Maria Leticia Zarantonelli, Gaëlle Tilly, Philippe Blancou, Gaëlle Bériou, Régis Josien, Ignacio Anegon, Eva Hong, Corinne Ruckly, Aude Antignac, Meriem El Ghachi, Ivo Gomperts Boneca, Muhamed-Kheir Taha, Maria Cristina Cuturi
المصدر: PLoS ONE, Vol 6, Iss 10, p e23995 (2011)
بيانات النشر: Public Library of Science (PLoS), 2011.
سنة النشر: 2011
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 µg/ml ± 0.1), CD80 (LOGEC50 = 4.88 µg/ml ± 0.15) and CD86 (LOGEC50 = 5.36 µg/ml ± 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 ± 5.1% cells versus 12 ± 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046231/?tool=EBI; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0023995
URL الوصول: https://doaj.org/article/61e725d987f74644a96064e4514e5ca7
رقم الأكسشن: edsdoj.61e725d987f74644a96064e4514e5ca7
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0023995