Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

Thay, Bernard; Damm, A.; Kufer, Thomas A.; Wai, Sun Nyunt; Oscarsson, Jan

doi:10.1128/iai.01980-14

Cited by 119 publications

(115 citation statements)

References 74 publications

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“…69). Similarly, A. actinomycetemcomitans OMVs induce NOD1-and NOD2-dependent responses in HEK293 cells and NOD1-driven inflammation in THP-1 myeloid cells 71 . Furthermore, V. cholerae OMVs induce NOD1-dependent production of CCL2 and CCL20 by epithelial cells 70 .…”

Section: Engagement Of Intracellular Prrsmentioning

confidence: 99%

Immune modulation by bacterial outer membrane vesicles

2015

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Gram-negative bacteria shed extracellular outer membrane vesicles (OMVs) during their normal growth both in vitro and in vivo. OMVs are spherical, bilayered membrane nanostructures that contain many components found within the parent bacterium. Until recently, OMVs were dismissed as a by-product of bacterial growth; however, findings within the past decade have revealed that both pathogenic and commensal bacteria can use OMVs to manipulate the host immune response. In this Review, we describe the mechanisms through which OMVs induce host pathology or immune tolerance, and we discuss the development of OMVs as innovative nanotechnologies.

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Section: Engagement Of Intracellular Prrsmentioning

confidence: 99%

Immune modulation by bacterial outer membrane vesicles

2015

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“…While the subcellular localization and expression of NOD1 and NOD2 vary depending on the cell type, the source and route of entry of the ligand also influence NOD1 and NOD2 complex formation. Indeed, outer membrane vesicles (OMVs) from a variety of bacteria (Irving et al, 2014; Thay et al, 2014) activate NOD1 and NOD2 signaling revealing an important role for vesicle internalization in the delivery of ligands to cytosolic NOD1 and NOD2 receptors. Given that soluble NOD1 and NOD2 ligands are sufficient to stimulate host cells there are clearly multiple routes for these molecules to enter the cell.…”

Section: Nod1 and Nod2: Ligand Recognition And Activationmentioning

confidence: 99%

NOD1 and NOD2: Signaling, Host Defense, and Inflammatory Disease

et al. 2014

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Summary The nucleotide-binding oligomerization domain (NOD) proteins, NOD1 and NOD2, the founding members of the intracellular NOD-like receptor family, sense conserved motifs in bacterial peptidoglycan and induce pro-inflammatory and anti-microbial responses. Here we discuss recent developments about the mechanisms by which NOD1 and NOD2 are activated by bacterial ligands, the regulation of their signaling pathways, and their role in host defense and inflammatory disease. Several routes for the entry of peptidoglycan ligands to the host cytosol to trigger activation of NOD1 and NOD2 have been elucidated. Furthermore, genetic screens and biochemical analyses have revealed mechanisms that regulate NOD1 and NOD2 signaling. Finally, recent studies suggest several mechanisms to account for the link between NOD2 mutations and susceptibility to Crohn’s disease. Further understanding of NOD1 and NOD2 should provide new insight into the pathogenesis of disease and the development of new strategies to treat inflammatory and infectious disorders.

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“…Other PRRs that respond to extracellular bacteria are localized in the cytosol, but their discovery prompted the question of how and why bacterial products translocate to the host cell cytosol. An explanation was provided by the demonstration that MVs produced by Helicobacter pylori, Pseudomonas aeruginosa, Neisseria gonorrhea, and Aggregatibacter actinomycetemcomitans contain peptidoglycan, fuse with host cell membranes, and activate NOD1/NOD2 (Kaparakis et al, 2010; Thay et al, 2014). More recently, it was demonstrated that enterohemorrhagic E. coli MVs traffic LPS to the cytosol of host cells and activate non-canonical inflammasome signaling (Vanaja et al, 2016).…”

Section: Immune Modulation By Bacterial Membrane Vesiclesmentioning

confidence: 99%

Interspecies Communication between Pathogens and Immune Cells via Bacterial Membrane Vesicles

Jurkoshek

Wang

Athman

et al. 2016

Front. Cell Dev. Biol.

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The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50–250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host. However, recent studies have also shown that bacterial MVs are enriched for molecules that stimulate innate and adaptive immune responses. As an example, MVs may serve multiple, important roles in regulating the host response to Mycobacterium tuberculosis (Mtb), an intracellular pathogen that infects lung macrophages and resides within modified phagosomes. Previously, we demonstrated that Mtb secretes MVs during infection that may modulate infected and uninfected immune cells. Our present data demonstrates that Mtb MVs inhibit the functions of macrophages and T cells, but promote Major Histocompatibility Complex (MHC) class II antigen presentation by dendritic cells. We conclude that bacterial MVs serve dual and opposing roles in the activation of and defense against host immune responses to Mtb and other bacterial pathogens. We also propose that MV secretion is a central mechanism for interspecies communication between bacteria and host cells during infection.

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Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

Cited by 119 publications

References 74 publications

Immune modulation by bacterial outer membrane vesicles

Immune modulation by bacterial outer membrane vesicles

NOD1 and NOD2: Signaling, Host Defense, and Inflammatory Disease

Interspecies Communication between Pathogens and Immune Cells via Bacterial Membrane Vesicles

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