Modulation of Gamma Interferon-Induced Major Histocompatibility Complex Class II Gene Expression by<i>Porphyromonas gingivalis</i>Membrane Vesicles

Srisatjaluk, Ratchapin; Kotwal, Girish J.; Hunt, Lawrence A.; Justus, David E.

doi:10.1128/iai.70.3.1185-1192.2002

Cited by 30 publications

(26 citation statements)

References 47 publications

(43 reference statements)

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“…Previous reports have shown that MVs possess various virulent abilities (9,13,25,39,40,43,48), while our results indicate a new aspect of cellular function impairment by P. gingivalis MVs.…”

Section: Discussionsupporting

confidence: 63%

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

2009

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Bacteria have evolved mechanisms for the secretion of virulence factors into host cells; these virulence factors alter host cell biology and enable bacterial colonization (11). Bacterial outer membrane vesicles (MVs), ubiquitously shed from gramnegative bacteria by a mechanism involving cell wall turnover, consist of a subset of outer membrane and soluble periplasmic components (54). This extracellular secretion system likely plays a part in the strategy utilized by bacterial pathogens to modulate host defense and response and impair host cell function. For example, Pseudomonas aeruginosa (3), Helicobacter pylori (19), and Actinobacillus actinomycetemcomitans (8), as well as pathogenic and nonpathogenic Escherichia coli (7, 51), secrete MVs that contain toxins, proteases, adhesins, and lipopolysaccharide. Therefore, it has been proposed that MVs are bacterial "bombs" (30). However, the molecular mechanism of MV entry into host cells is unclear, while it also remains unknown whether MV-associated virulence factors have cytotoxic effects within the invaded cells. A recent study showed that enterotoxigenic E. coli MVs containing heat-labile enterotoxin and other bacterial envelope components were taken up by a human epithelial cell line via cellular lipid rafts, after which intracellular MVs accumulated in nonacidified compartments inaccessible to the extracellular milieu (28). In addition, a very recent study found that Pseudomonas aeruginosa MVs deliver multiple virulence factors, including ␤-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif (cystic fibrosis transmembrane conductance regulator inhibitory factor), directly into the host cytoplasm via fusion of MVs with lipid rafts in the host plasma membrane, which has an effect on host cell biology (5). Thus, it is likely MVs function as specifically targeted transport vehicles to mediate entry of bacterial virulence factors into host cells. However, no other related results have been reported.Periodontitis, one of the most common infectious diseases seen in humans (52), is characterized by gingival inflammation, as well as loss of connective tissue and bone from around the roots of the teeth, which leads to eventual tooth exfoliation. Porphyromonas gingivalis is considered to be a bona fide pathogen that causes several forms of severe periodontal disease. The bacterium releases MVs in an extracellular manner; these MVs retain the full components of outer membrane constituents, including lipopolysaccharide, muramic acid, a capsule, fimbriae, and proteases termed gingipains (13,35). Fimbriae reportedly mediate bacterial adherence to and entry into periodontal cells (2), while gingipains, which consist of arginine (Arg-gingipain [Rgp])-and lysine (Lys-gingipain [Kgp])-specific cysteine proteinases, contribute to the destruction of periodontal tissues (24). Gingipains degrade collagen and fibronectin and inhibit interactions between host cells and the extracellular matrix. In addition, they degrade various cytokines, resulting in a disturbance of t...

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Section: Discussionsupporting

confidence: 63%

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

2009

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“…In addition, MVs have been reported to possess various virulent abilities (9,13,21,39,41,47,51). We intend to conduct additional studies to elucidate the cellular functions impaired by invading MVs.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments

et al. 2009

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Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including major fimbriae and proteases termed gingipains, although it is not confirmed whether MVs enter host cells. In this study, we analyzed the mechanisms involved in the interactions of P. gingivalis MVs with human epithelial cells. Our results showed that MVs swiftly adhered to HeLa and immortalized human gingival epithelial cells in a fimbria-dependent manner and then entered via a lipid raft-dependent endocytic pathway. The intracellular MVs were subsequently routed to early endosome antigen 1-associated compartments and then were sorted to lysosomal compartments within 90 min, suggesting that intracellular MVs were ultimately degraded by the cellular digestive machinery. However, P. gingivalis MVs remained there for over 24 h and significantly induced acidified compartment formation after being taken up by the cellular digestive machinery. In addition, MV entry was shown to be mediated by a novel pathway for transmission of bacterial products into host cells, a Rac1-regulated pinocytic pathway that is independent of caveolin, dynamin, and clathrin. Our findings indicate that P. gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis.

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“…Neisseria vesicles have been proposed to act as decoys to the immune system, binding and removing cell-targeted bactericidal factors in serum (Pettit and Judd 1992). The gingipain proteases on P. gingivalis vesicles cause CD14 degradation on O937 human macrophages that could lead to disarming the responsiveness of the immune system in periodontal disease (Duncan et al 2004) P. gingivalis vesicles also induce membrane expression of E-selectin and ICAM-1 on vascular endothelial cells, whereas they inhibit synthesis of interferon ␥ MHC class II synthesis (Srisatjaluk et al 1999(Srisatjaluk et al , 2002.…”

Section: Modulation Of Host Responsementioning

confidence: 99%

Bacterial outer membrane vesicles and the host–pathogen interaction

Kuehn¹,

Kesty²

2005

Genes Dev.

774

707

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Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors. Vesicles play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response. Vesicle-mediated toxin delivery is a potent virulence mechanism exhibited by diverse Gram-negative pathogens. The biochemical and functional properties of pathogen-derived vesicles reveal their potential to critically impact disease.In nearly every case, virulence factors of Gram-negative pathogens are secreted products that enhance the survival of the bacteria and/or damage the host. Secretion of virulence factors by Gram-negative pathogens is complicated by the fact that the bacterial envelope consists of two lipid bilayers, the inner and outer membrane, and the periplasm in between. Gram-negative pathogens have developed many strategies, some specific to pathogens, to enable active virulence factors to gain access to the extracellular environment, typically the tissues or bloodstream of the host organism (Henderson et al. 2004). The Type II and Type V secretion systems are two-step processes in which proteins are transported first through the inner membrane (IM) and then through the outer membrane (OM). For secretion via the Type I, Type III, and Type IV secretion systems, the material is transferred directly into the extracellular milieu or into another cell. The Type III system is specific for the transport of factors by pathogenic bacteria. All of these secretion systems secrete individual proteins or small complexes. This review examines secretion via OM vesicles, a distinct "Type VI" mechanism that enables bacteria to secrete a large, complex group of proteins and lipids into the extracellular milieu.Both pathogenic and nonpathogenic species of Gram- Vesicles are a means by which bacteria interact with prokaryotic and eukaryotic cells in their environment. Some of the best-characterized vesicles are those produced by pathogens. Biochemical analysis and functional characterization of pathogen-derived outer membrane vesicles demonstrate that this secretory pathway has been usurped by pathogens for the transport of active virulence factors to host cells (Table 1). Naturally produced OM vesicles from pathogenic bacteria contain adhesins, toxins, and immunomodulatory compounds, and they directly mediate bacterial binding and invasion, cause cytotoxicity, and modulate the host immune response. By participating in such diverse aspects of the host-pathogen interaction, OM vesicles are potent bacterial virulence factors. Formation of bacterial OM vesiclesNaturally produced bacterial vesicles are discrete, closed OM blebs produced by growing cells, not products of cell lysis or cell death (Mug-Opstelte...

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Modulation of Gamma Interferon-Induced Major Histocompatibility Complex Class II Gene Expression byPorphyromonas gingivalisMembrane Vesicles

Abstract: Gamma interferon (IFN-␥)-induced endothelial cells actively participate in initiating immune responses by interacting with CD4؉ T cells via class II major histocompatibility complex (

Cited by 30 publications

References 47 publications

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

Entry ofPorphyromonas gingivalisOuter Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments

Bacterial outer membrane vesicles and the host–pathogen interaction

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