Polymorphic Membrane Protein (PMP) 20 and PMP 21 of<i>Chlamydia pneumoniae</i>Induce Proinflammatory Mediators in Human Endothelial Cells In Vitro by Activation of the Nuclear Factor‐κB Pathway

Niessner, Alexander; Kaun, Christoph; Zorn, Gerlinde; Speidl, Walter S.; Türel, Zeynep; Christiansen, Gunna; Pedersen, Anna-Sofie; Birkelund, Svend; Simon, Susan; Georgopoulos, Apostolos P.; Graninger, Wolfgang; Martin, Rainer de; Lipp, Joachim; Binder, Bernd R.; Maurer, Gerald; Huber, Kurt; Wojta, Johann

doi:10.1086/375827

Cited by 40 publications

(28 citation statements)

References 36 publications

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“…Moreover, examination of the role of the POMPs in triggering an immune response recently demonstrated that Pmp20 and Pmp21 from C. pneumoniae could increase the production of the inflammatory mediators IL-6, IL-8 and monocyte chemoattractant protein 1 in a dose-dependent fashion in cultured human endothelial cells. Furthermore, this induction was due to the activation of the nuclear factor B pathway (353). It was suggested that by interaction of the POMPs with the endothelium, the POMPs contribute to vascular injury and thus to the development and progression of atherosclerotic lesions, which are associated with infection by several organisms from the Chlamydiaceae.…”

Section: Cluster 7: Chlamydial Autotransportersmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

712

795

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Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

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Section: Cluster 7: Chlamydial Autotransportersmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

712

795

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“…Besides the serologically defined and molecularly characterized chlamydial Ags recognized during human infection (6,24,25), recent advances in chlamydial genomics have predicted several immunogenic proteins (26 -28) that may serve as potential vaccine candidates. The most prominent among these to date include the polymorphic OMPs (29) (30,31), the conserved PorB family of membrane proteins (32)(33)(34), and the ADP/ATP translocase of Chlamydia pneumoniae (26,27).…”

Section: G Enital Infection With the Obligate Intracellular Bacteriummentioning

confidence: 99%

A Novel Recombinant Multisubunit Vaccine against Chlamydia

Eko

Brown

et al. 2004

The Journal of Immunology

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The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues. We investigated the hypothesis that rVCG could serve as effective delivery vehicles for single or multiple subunit chlamydial vaccines to induce a high level of protective immunity. rVCG-expressing chlamydial outer membrane proteins were produced by a two-step genetic process, involving cloning of Omp genes in V. cholerae, followed by gene E-mediated lysis of the cells. The immunogenicity and vaccine efficacy of rVCG-expressing single and multiple subunits were compared. Immunologic analysis indicated that i.m. immunization of mice with either vaccine construct induced a strong mucosal and systemic specific Th1 response against the whole chlamydial organism. However, there was an immunogenic advantage associated with the multiple subunit vaccine that induced a higher frequency of Th1 cells and a relatively greater ability to confer protective immunity, compared with the single subunit construct. These results support the operational theory that the ability of a vaccine to confer protective immunity against Chlamydia is a function of the level of Th1 response elicited.

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“…Furthermore, recombinant C. pneumoniae PmpD has been suggested to function as an adhesin capable of inducing proinflammatory cytokine production (35,52). Nothing is known about the native structure of C. trachomatis PmpD or the potential significance of its structure to chlamydial pathogenesis.…”

mentioning

confidence: 99%

Chlamydia trachomatisPolymorphic Membrane Protein D Is an Oligomeric Autotransporter with a Higher-Order Structure

et al. 2009

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Chlamydia trachomatis is a globally important obligate intracellular bacterial pathogen that is a leading cause of sexually transmitted disease and blinding trachoma. Effective control of these diseases will likely require a preventative vaccine. C. trachomatis polymorphic membrane protein D (PmpD) is an attractive vaccine candidate as it is conserved among C. trachomatis strains and is a target of broadly cross-reactive neutralizing antibodies. We show here that immunoaffinity-purified native PmpD exists as an oligomer with a distinct 23-nm flower-like structure. Two-dimensional blue native-sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed that the oligomers were composed of full-length PmpD (p155) and two proteolytically processed fragments, the p73 passenger domain (PD) and the p82 translocator domain. We also show that PmpD undergoes an infection-dependent proteolytic processing step late in the growth cycle that yields a soluble extended PD (p111) that was processed into a p73 PD and a novel p30 fragment. Interestingly, soluble PmpD peptides possess putative eukaryote-interacting functional motifs, implying potential secondary functions within or distal to infected cells. Collectively, our findings show that PmpD exists as two distinct forms, a surface-associated oligomer exhibiting a higher-order flower-like structure and a soluble form restricted to infected cells. We hypothesize that PmpD is a multifunctional virulence factor important in chlamydial pathogenesis and could represent novel vaccine or drug targets for the control of human chlamydial infections.Chlamydia trachomatis is a mucosotropic obligate intracellular gram-negative pathogen that is a leading cause of sexually transmitted and ocular infections. Infection can result in serious sequelae such as infertility and blindness (54, 56) and an increased risk of human immunodeficiency virus infection and transmission (38). The pathophysiology of chlamydial infection is associated with the pathogen's propensities to cause persistent infection and to suppress host immunity (3). A vaccine is needed to control chlamydial diseases; however, progress toward this goal will not be forthcoming until more is known about the virulence factors that mediate persistence and immune evasion.Chlamydiae are characterized by a unique biphasic developmental cycle that modulates between an extracellular, metabolically inactive, infectious elementary body (EB) and an intracellular, metabolically active, noninfectious reticulate body (RB) (34). Their obligate intracellular niche and the lack of a tractable genetic system present unique challenges in the study of chlamydial biology and pathogenesis. To overcome these hurdles, chlamydial genomes from a diverse spectrum of hostspecific strains have been sequenced. Comparative genomics have shown considerable homology among various chlamydial species and have provided important insights into shared and species-specific virulence factors (7,24,41,42,46,49).The type V or autotransporter (AT) secretion p...

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Polymorphic Membrane Protein (PMP) 20 and PMP 21 ofChlamydia pneumoniaeInduce Proinflammatory Mediators in Human Endothelial Cells In Vitro by Activation of the Nuclear Factor‐κB Pathway

Cited by 40 publications

References 36 publications

Type V Protein Secretion Pathway: the Autotransporter Story

Type V Protein Secretion Pathway: the Autotransporter Story

A Novel Recombinant Multisubunit Vaccine against Chlamydia

Chlamydia trachomatisPolymorphic Membrane Protein D Is an Oligomeric Autotransporter with a Higher-Order Structure

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