Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4.
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 dendr...
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2011
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oai:doaj.org-article:61e725d987f74644a96064e4514e5ca72021-11-18T07:35:38ZPenicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4.1932-620310.1371/journal.pone.0023995https://doaj.org/article/61e725d987f74644a96064e4514e5ca72011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046231/?tool=EBIhttps://doaj.org/toc/1932-6203Neisseria 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.Marcelo HillAla-Eddine DeghmaneMercedes SegoviaMaria Leticia ZarantonelliGaëlle TillyPhilippe BlancouGaëlle BériouRégis JosienIgnacio AnegonEva HongCorinne RucklyAude AntignacMeriem El GhachiIvo Gomperts BonecaMuhamed-Kheir TahaMaria Cristina CuturiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e23995 (2011) |
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| collection |
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| language |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Marcelo Hill |
| title |
Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| title_short |
Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| title_full |
Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| title_fullStr |
Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| title_full_unstemmed |
Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. |
| title_sort |
penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through toll-like receptor 4. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/61e725d987f74644a96064e4514e5ca7 |
| work_keys_str_mv |
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