Dataset Information

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction.

ABSTRACT: Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles. Intraepithelial HIV-1 remained infectious for 9 days without viral release. Release of sequestered intraepithelial HIV-1 was induced by the calcium ionophore ionomycin and by cytochalasin D, which increase intracellular calcium and disrupt the cortical actin of epithelial cells, respectively. Cocultivation of epithelial cells containing HIV-1 with activated peripheral blood mononuclear cells and CD4+ T lymphocytes led to the disruption of epithelial cortical actin and spread of virus from epithelial cells to lymphocytes. Treatment of epithelial cells with proinflammatory cytokines tumor necrosis factor-alpha and interferon gamma also induced reorganization of cortical actin and release of virus. Inhibition of MVB formation by small interfering RNA (siRNA)-mediated silencing of its critical protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced viral sequestration in epithelial cells and its transmission from epithelial cells to lymphocytes by ~60-70%. Furthermore, inhibition of vacuole formation of epithelial cells by siRNA-inactivated rabankyrin-5 expression also significantly reduced HIV-1 sequestration in epithelial cells and spread of virus from epithelial cells to lymphocytes. Interaction of the intercellular adhesion molecule-1 of epithelial cells with the function-associated antigen-1 of lymphocytes was important for inducing the release of sequestered HIV-1 from epithelial cells and facilitating cell-to-cell spread of virus from epithelial cells to lymphocytes. This mechanism may serve as a pathway of HIV-1 mucosal transmission.

SUBMITTER: Yasen A

PROVIDER: S-EPMC5344537 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction.

Yasen Aizezi A Herrera Rossana R Rosbe Kristina K Lien Kathy K Tugizov Sharof M SM

PLoS pathogens 20170227 2

Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. ...[more]

PMID: 28241053

Similar Datasets

Project description:Cellular Phenotype and Apoptosis: The function of epithelial tissues is the protection of the organism from chemical, microbial, and physical challenges which is indispensable for viability. To fulfill this task, oral epithelial cells follow a strongly regulated scheme of differentiation that results in the formation of structural proteins that manage the integrity of epithelial tissues and operate as a barrier. Oral epithelial cells are connected by various transmembrane proteins with specialized structures and functions. Keratin filaments adhere to the plasma membrane by desmosomes building a three-dimensional matrix. Cell-Cell Contacts and Bacterial Influence: It is known that pathogenic oral bacteria are able to affect the expression and configuration of cell-cell junctions. Human keratinocytes up-regulate immune-modulatory receptors upon stimulation with bacterial components. Periodontal pathogens including P. gingivalis are able to inhibit oral epithelial innate immune responses through various mechanisms and to escape from host immune reaction, which supports the persistence of periodontitis and furthermore is able to affect the epithelial barrier function by altering expression and distribution of cell-cell interactions including tight junctions (TJs) and adherens junctions (AJs). In the pathogenesis of periodontitis a highly organized biofilm community shifts from symbiosis to dysbiosis which results in destructive local inflammatory reactions. Cellular Receptors: Cell-surface located toll like receptors (TLRs) and cytoplasmatic nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) belong to the pattern recognition receptors (PRRs). PRRs recognize microbial parts that represent pathogen-associated molecular patterns (PAMPs). A multimeric complex of proteins known as inflammasome, which is a subset of NLRs, assembles after activation and proceeds to pro-inflammatory cytokine release. Cytokine Production and Release: Cytokines and bacterial products may lead to host cell mediated tissue destruction. Keratinocytes are able to produce diverse pro-inflammatory cytokines and chemokines, including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-?. Infection by pathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) can induce a differentiated production of these cytokines. Immuno-modulation, Bacterial Infection, and Cancer Cells: There is a known association between bacterial infection and cancer. Bacterial components are able to up-regulate immune-modulatory receptors on cancer cells. Interactions of bacteria with tumor cells could support malignant transformation an environment with deficient immune regulation. The aim of this review is to present a set of molecular mechanisms of oral epithelial cells and their reactions to a number of toxic influences.

Project description:Introduction:Carrier-free autologous mucosal epithelial cell sheets have been clinically utilized as a cell therapy for various epithelial disorders. Fabrication of a transplantable oral mucosal epithelial cell sheet without mouse feeder layers requires a higher seeding density than that of a sheet with mouse feeder layer culture; therefore, a large amount of donor mucosal tissue is needed. However, cell grafts co-cultured with mouse feeder layers are classified by the US Food and Drug Administration (FDA) as xenogeneic products. The goal of this study was to evaluate the utility of oral mucosal epithelial cells expanded by primary explant culture for the fabrication of an adequate number of transplantable epithelial cell sheets without mouse feeder layers. Methods:Small fragments derived from minced oral mucosal tissue were placed into culture dishes for primary explant culture in keratinocyte culture medium. After primary explant culture, the outgrown cells were treated with trypsin-EDTA and were seeded on a temperature-responsive cell culture insert. After subculture, the cultured cells were harvested as a confluent cell sheet from the culture vessel by temperature reduction. Results:Carrier-free human oral mucosal epithelial cell sheets were fabricated in all human cases, and autologous transplantation of the harvested cell sheets showed rapid epithelial regeneration to cover epithelial defects in a rabbit model. The explant culture method, involving the use of small fragments for primary culture, was sufficient for preparing a large number of mucosal epithelial cells without mouse feeder layers. Moreover, oral mucosal epithelial cells derived from the primary explant culture after cryopreservation allowed for the fabrication of cell sheets. Conclusions:This method for fabricating transplantable oral mucosal epithelial cell sheets is an attractive technique for regenerative medicine. It offers a patient-friendly manufacturing method in which a small amount of biopsy material from the patient represents a sufficient epithelial cell source, and a manufacturing plan for preparing cell grafts can be easily tailored.

Dataset Information

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction.

Publications

Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets