Universität zu Köln

Thay, Bernard, Damm, Anna, Kufer, Thomas A., Wai, Sun Nyunt and Oscarsson, Jan (2014). Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-kappa B Activation. Infect. Immun., 82 (10). S. 4034 - 4047. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5522

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Abstract

Aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. We recently demonstrated that outer membrane vesicles (OMVs) disseminated by A. actinomycetemcomitans could deliver multiple proteins, including biologically active cytolethal distending toxin (CDT), into the cytosol of HeLa cells and human gingival fibroblasts (HGF). In the present work, we have used immunoelectron and confocal microscopy analysis and fluorescently labeled vesicles to further investigate mechanisms for A. actinomycetemcomitans OMV-mediated delivery of bacterial antigens to these host cells. Our results supported that OMVs were internalized into the perinuclear region of HeLa cells and HGF. Colocalization analysis revealed that internalized OMVs colocalized with the endoplasmic reticulum and carried antigens, detected using an antibody specific to whole A. actinomycetemcomitans serotype a cells. Consistent with OMV internalization mediating intracellular antigen exposure, the vesicles acted as strong inducers of cytoplasmic peptidoglycan sensor NOD1-and NOD2-dependent NF-kappa B activation in human embryonic kidney cells. Moreover, NOD1 was the main sensor of OMV-delivered peptidoglycan in myeloid THP1 cells, contributing to the overall inflammatory responses induced by the vesicles. This work reveals a role of A. actinomycetemcomitans OMVs as a trigger of innate immunity via carriage of NOD1- and NOD2-active pathogen-associated molecular patterns (PAMPs).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thay, Bernard UNSPECIFIED UNSPECIFIED UNSPECIFIED Damm, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Kufer, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wai, Sun Nyunt UNSPECIFIED UNSPECIFIED UNSPECIFIED Oscarsson, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428071
DOI:	10.1128/IAI.01980-14
Journal or Publication Title:	Infect. Immun.
Volume:	82
Number:	10
Page Range:	S. 4034 - 4047
Date:	2014
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5522
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOLETHAL DISTENDING TOXIN; PERIODONTAL-LIGAMENT CELLS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; EPITHELIAL-CELLS; ESCHERICHIA-COLI; BACTERIAL PEPTIDOGLYCAN; GINGIVAL FIBROBLASTS; BONE LOSS; LEUKOTOXIN; INDUCTION Multiple languages Immunology; Infectious Diseases Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42807