B cell activation by outer membrane vesicles--a novel virulence mechanism.

Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce...

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Autores principales:	Maria Laura A Perez Vidakovics, Johan Jendholm, Matthias Mörgelin, Anne Månsson, Christer Larsson, Lars-Olaf Cardell, Kristian Riesbeck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9e34a60422e64053823e5a9945e54a14
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spelling	oai:doaj.org-article:9e34a60422e64053823e5a9945e54a142021-11-25T05:48:22ZB cell activation by outer membrane vesicles--a novel virulence mechanism.1553-73661553-737410.1371/journal.ppat.1000724https://doaj.org/article/9e34a60422e64053823e5a9945e54a142010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20090836/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent B cell response by the immunoglobulin (Ig) D-binding superantigen MID. Here we demonstrate that Moraxella are endocytosed and killed by human tonsillar B cells, whereas OMV have the potential to interact and activate B cells leading to bacterial rescue. The B cell response induced by OMV begins with IgD B cell receptor (BCR) clustering and Ca(2+) mobilization followed by BCR internalization. In addition to IgD BCR, TLR9 and TLR2 were found to colocalize in lipid raft motifs after exposure to OMV. Two components of the OMV, i.e., MID and unmethylated CpG-DNA motifs, were found to be critical for B cell activation. OMV containing MID bound to and activated tonsillar CD19(+) IgD(+) lymphocytes resulting in IL-6 and IgM production in addition to increased surface marker density (HLA-DR, CD45, CD64, and CD86), whereas MID-deficient OMV failed to induce B cell activation. DNA associated with OMV induced full B cell activation by signaling through TLR9. Importantly, this concept was verified in vivo, as OMV equipped with MID and DNA were found in a 9-year old patient suffering from Moraxella sinusitis. In conclusion, Moraxella avoid direct interaction with host B cells by redirecting the adaptive humoral immune response using its superantigen-bearing OMV as decoys.Maria Laura A Perez VidakovicsJohan JendholmMatthias MörgelinAnne MånssonChrister LarssonLars-Olaf CardellKristian RiesbeckPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 1, p e1000724 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Maria Laura A Perez Vidakovics Johan Jendholm Matthias Mörgelin Anne Månsson Christer Larsson Lars-Olaf Cardell Kristian Riesbeck B cell activation by outer membrane vesicles--a novel virulence mechanism.
description	Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent B cell response by the immunoglobulin (Ig) D-binding superantigen MID. Here we demonstrate that Moraxella are endocytosed and killed by human tonsillar B cells, whereas OMV have the potential to interact and activate B cells leading to bacterial rescue. The B cell response induced by OMV begins with IgD B cell receptor (BCR) clustering and Ca(2+) mobilization followed by BCR internalization. In addition to IgD BCR, TLR9 and TLR2 were found to colocalize in lipid raft motifs after exposure to OMV. Two components of the OMV, i.e., MID and unmethylated CpG-DNA motifs, were found to be critical for B cell activation. OMV containing MID bound to and activated tonsillar CD19(+) IgD(+) lymphocytes resulting in IL-6 and IgM production in addition to increased surface marker density (HLA-DR, CD45, CD64, and CD86), whereas MID-deficient OMV failed to induce B cell activation. DNA associated with OMV induced full B cell activation by signaling through TLR9. Importantly, this concept was verified in vivo, as OMV equipped with MID and DNA were found in a 9-year old patient suffering from Moraxella sinusitis. In conclusion, Moraxella avoid direct interaction with host B cells by redirecting the adaptive humoral immune response using its superantigen-bearing OMV as decoys.
format	article
author	Maria Laura A Perez Vidakovics Johan Jendholm Matthias Mörgelin Anne Månsson Christer Larsson Lars-Olaf Cardell Kristian Riesbeck
author_facet	Maria Laura A Perez Vidakovics Johan Jendholm Matthias Mörgelin Anne Månsson Christer Larsson Lars-Olaf Cardell Kristian Riesbeck
author_sort	Maria Laura A Perez Vidakovics
title	B cell activation by outer membrane vesicles--a novel virulence mechanism.
title_short	B cell activation by outer membrane vesicles--a novel virulence mechanism.
title_full	B cell activation by outer membrane vesicles--a novel virulence mechanism.
title_fullStr	B cell activation by outer membrane vesicles--a novel virulence mechanism.
title_full_unstemmed	B cell activation by outer membrane vesicles--a novel virulence mechanism.
title_sort	b cell activation by outer membrane vesicles--a novel virulence mechanism.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/9e34a60422e64053823e5a9945e54a14
work_keys_str_mv	AT marialauraaperezvidakovics bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT johanjendholm bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT matthiasmorgelin bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT annemansson bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT christerlarsson bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT larsolafcardell bcellactivationbyoutermembranevesiclesanovelvirulencemechanism AT kristianriesbeck bcellactivationbyoutermembranevesiclesanovelvirulencemechanism
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B cell activation by outer membrane vesicles--a novel virulence mechanism.

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