scholarly journals Low-Phosphate-Dependent Invasion Resembles a General Way for Neisseria gonorrhoeae To Enter Host Cells

2006 ◽  
Vol 74 (7) ◽  
pp. 4266-4273 ◽  
Author(s):  
Christiane Kühlewein ◽  
Cindy Rechner ◽  
Thomas F. Meyer ◽  
Thomas Rudel
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Rho Gtpases ◽  
Wide Spectrum ◽  
Cell Types ◽  
Surface Proteins ◽  
Host Cells ◽  
Animal Origin ◽  
Target Cells ◽  
Pit Formation ◽  
Serious Disease

ABSTRACT Obligate human-pathogenic Neisseria gonorrhoeae expresses numerous variant surface proteins mediating adherence to and invasion of target cells. The invariant major outer membrane porin PorB of serotype A (P.IA) gonococci triggers invasion into Chang cells only if the medium is devoid of phosphate. Since gonococci expressing PorBIA are frequently isolated from patients with severe disseminating infections, the interaction initiated by the porin may be of major relevance for the development of this serious disease. Here, we investigated the low-phosphate-dependent invasion and compared it to the well-known pathways of entry initiated by Opa proteins. P.IA-triggered invasion requires clathrin-coated pit formation and the action of actin and Rho GTPases. However, in contrast to Opa-initiated invasion via heparan sulfate proteoglycans, microtubules, acidic sphingomyelinase, phosphatidylinositol 3-kinase, and myosin light chain kinase are not involved in this entry pathway. Nor are Src kinases required, as they are in invasion, e.g., via the CEACAM3 receptor. Invasion by PorBIA occurs in a wide spectrum of cell types, such as primary human epithelial and endothelial cells and in cancer cells of human and animal origin. Low-phosphate-dependent invasion is thus a pathway of gonococcal entry distinct from Opa-mediated invasion.

Biochemical and cellular mechanisms regulatingAcanthamoeba castellaniiadherence to host cells

Parasitology ◽  
2013 ◽  
Vol 141 (4) ◽  
pp. 531-541 ◽  
Author(s):  
K. J. SOTO-ARREDONDO ◽  
L. L. FLORES-VILLAVICENCIO ◽  
J. J. SERRANO-LUNA ◽  
M. SHIBAYAMA ◽  
M. SABANERO-LÓPEZ
Keyword(s):  
Neuronal Cells ◽  
Acanthamoeba Castellanii ◽  
Cell Types ◽  
Infection Process ◽  
Surface Proteins ◽  
Host Cells ◽  
Epifluorescence Microscopy ◽  
Cellular Mechanisms ◽  
Cutaneous Lesions ◽  
Causative Agents

SUMMARYFree-living amoebae belonging to the genusAcanthamoebaare the causative agents of infections such as amoebic keratitis (AK), granulomatous amoebic encephalitis (GAE) and cutaneous lesions. The mechanisms involved in the establishment of infection are unknown. However, it is accepted that the initial phase of pathogenesis involves adherence to the host tissue. In this work, we analysed surface molecules with an affinity for epithelial and neuronal cells from the trophozoites ofAcanthamoeba castellanii. We also investigated the cellular mechanisms that govern the process of trophozoite adhesion to the host cells. We first used confocal and epifluorescence microscopy to examine the distribution of theA. castellaniiactin cytoskeleton during interaction with the host cells. The use of drugs, as cytochalasin B (CB) and latrunculin B (LB), revealed the participation of cytoskeletal filaments in the adhesion process. In addition, to identify the proteins and glycoproteins on the surface ofA. castellanii, the trophozoites were labelled with biotin and biotinylated lectins. The results revealed bands of surface proteins, some of which were glycoproteins with mannose andN-acetylglucosamine residues. Interaction assays of biotinylated amoebae proteins with epithelial and neuronal cells showed that some surface proteins had affinity for both cell types. The results of this study provide insight into the biochemical and cellular mechanisms of theAcanthamoebainfection process.

A circulating microvesicle-based biosignature for the detection of colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 373-373 ◽  
Author(s):  
D. Spetzler ◽  
T. Tinder ◽  
S. Kankipati ◽  
M. Maheshwari ◽  
C. D. Kuslich
Keyword(s):  
Colorectal Cancer ◽  
Surface Membrane ◽  
Stage Iv ◽  
Target Surface ◽  
Cell Types ◽  
Surface Proteins ◽  
Target Cells ◽  
Cell Of Origin ◽  
Protein Biomarkers ◽  
Multiplexed Immunoassay

373 Background: Microvesicles are principally derived either from the endosomal pathway (as exosomes) or shed directly from the plasma membrane. They are between 40-500 nm in diameter and are secreted by most cell types, including tumor cells. In circulation, microvesicles appear to participate in cellular communication by transporting mRNAs, miRs and proteins from their cell of origin to target cells where they can elicit biological responses. The quantity and protein topography of microvesicles shed from cancer cells varies considerably compared to those shed from normal cells. Thus, the concentration of circulating plasma microvesicles with molecular markers indicative of the disease state can be used as a robust and informative blood-based biosignature. In this study we report the results of the application of a novel multiplexed method for quantifying and profiling microvesicles in plasma for the detection of colorectal cancer. Methods: We have developed a versatile mulitplexed microvesicle-based discovery panel with 73 different antibodies that target surface proteins of various microvesicle subpopulations. This system was used to develop a microvesicle-derived biosignature composed of 2 different surface membrane protein biomarkers. Results: In this study, we demonstrate that a combination of TMEM211 and CD24 provide a robust signature for the detection of colorectal cancer (CRC). We isolated microvesicles from plasma of 257 patients with CRC, 57 stage I, 104 stage II, 80 stage 3, 6 stage IV, and 11 of unknown stage; 327 self-described, age-range matched normal plasma specimens were used for the control population. The level of TMEM211 and CD24 containing microvesicles for these samples was determined using a multiplexed immunoassay. Thresholds were empirically determined to maximize the sensitivity and specificity of CRC detection, resulting in a sensitivity of 90% with a specificity of 85% with an AUC of .91. Conclusions: This study demonstrates that it is possible to use circulating microvesicles for the development of a highly sensitive and specific blood-based assay to detect CRC. [Table: see text]

scholarly journals Development of an Avian Leukosis-Sarcoma Virus Subgroup A Pseudotyped Lentiviral Vector

2001 ◽  
Vol 75 (19) ◽  
pp. 9339-9344 ◽  
Author(s):  
Brian C. Lewis ◽  
Nachimuthu Chinnasamy ◽  
Richard A. Morgan ◽  
Harold E. Varmus
Keyword(s):  
Transgenic Mice ◽  
Lentiviral Vector ◽  
Transgenic Animals ◽  
Cell Types ◽  
Host Cells ◽  
Target Cells ◽  
Mouse Tumor ◽  
Sarcoma Virus ◽  
Hiv 1

ABSTRACT We are using avian leukosis-sarcoma virus (ALSV) vectors to generate mouse tumor models in transgenic mice expressing TVA, the receptor for subgroup A ALSV. Like other classical retroviruses, ALSV requires cell division to establish a provirus after infection of host cells. In contrast, lentiviral vectors are capable of integrating their viral DNA into the genomes of nondividing cells. With the intention of initiating tumorigenesis in resting, TVA-positive cells, we have developed a system for the preparation of a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector, pseudotyped with the envelope protein of ALSV subgroup A (EnvA). The HIV(ALSV-A) vector retains the requirement for TVA on the surface of target cells and can be produced at titers of 5 × 103 infectious units (IU)/ml. By inserting the central polypurine tract (cPPT) from the HIV-1 pol gene and removing the cytoplasmic tail of EnvA, the pseudotype can be produced at titers approaching 105 IU/ml and can be concentrated by ultracentrifugation to titers of 107 IU/ml. HIV(ALSV-A) also infects embryonic fibroblasts derived from transgenic mice in which TVA expression is driven by the β-actin promoter. In addition, this lentivirus pseudotype efficiently infects these fibroblasts after cell cycle arrest, when they are resistant to infection by ALSV vectors. This system may be useful for introducing genes into somatic cells in adult TVA transgenic animals and allows evaluation of the effects of altered gene expression in differentiated cell types in vivo.

scholarly journals Regulation of Growth Cone Actin Dynamics by ADF/Cofilin

2003 ◽  
Vol 51 (4) ◽  
pp. 411-420 ◽  
Author(s):  
Ravine A. Gungabissoon ◽  
James R. Bamburg
Keyword(s):  
Actin Cytoskeleton ◽  
Growth Cone ◽  
Rho Gtpases ◽  
System Development ◽  
Cell Types ◽  
Growth Cones ◽  
Nervous System Development ◽  
Actin Dynamics ◽  
Target Cells ◽  
Lim Kinase

Nervous system development is reliant on neuronal pathfinding, the process in which axons are guided to their target cells by specific extracellular cues. The ability of neurons to extend over long distances in response to environmental guidance signals is made possible by the growth cone, a highly motile structure found at the end of neuronal processes. Growth cones detect directional cues and respond with either attractive or repulsive movements. The motility of growth cones is dependent on rapid reorganization of the actin cytoskeleton, presumably mediated by actin-associated proteins under the control of incoming guidance signals. This article reviews how one such family of proteins, the ADF/cofilins, are emerging as key regulators of growth cone actin dynamics. These proteins are essential for rapid actin turnover in a variety of different cell types. ADF/cofilins are heavily co-localized with actin in growth cones and are necessary for neurite outgrowth. ADF/cofilin activities are regulated through reversible phosphorylation by LIM kinases and slingshot phosphatases. LIM kinases are downstream effectors of the Rho GTPases Rho, Rac, and Cdc42. Growing evidence suggests that extracellular guidance cues may locally alter actin dynamics by regulating the activity of LIM kinase and ADF/cofilin phosphatases via the Rho GTPases. In this way, ADF/cofilins and their upstream effectors may be pivotal to our understanding of how guidance information is translated into physical alterations of the growth cone actin cytoskeleton.

scholarly journals Delivery of Toxins and Effectors by Bacterial Membrane Vesicles

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 845
Author(s):  
Adrian Macion ◽  
Agnieszka Wyszyńska ◽  
Renata Godlewska
Keyword(s):  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Oral Bacteria ◽  
Host Cells ◽  
Target Cells ◽  
Tissue Destruction ◽  
Secretion Systems ◽  
The Central Nervous System

Pathogenic bacteria interact with cells of their host via many factors. The surface components, i.e., adhesins, lipoproteins, LPS and glycoconjugates, are particularly important in the initial stages of colonization. They enable adhesion and multiplication, as well as the formation of biofilms. In contrast, virulence factors such as invasins and toxins act quickly to damage host cells, causing tissue destruction and, consequently, organ dysfunction. These proteins must be exported from the bacterium and delivered to the host cell in order to function effectively. Bacteria have developed a number of one- and two-step secretion systems to transport their proteins to target cells. Recently, several authors have postulated the existence of another transport system (sometimes called “secretion system type zero”), which utilizes extracellular structures, namely membrane vesicles (MVs). This review examines the role of MVs as transporters of virulence factors and the interaction of toxin-containing vesicles and other protein effectors with different human cell types. We focus on the unique ability of vesicles to cross the blood–brain barrier and deliver protein effectors from intestinal or oral bacteria to the central nervous system.

scholarly journals Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

Gut ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1010-1018 ◽  
Author(s):  
Hao Zhang ◽  
Zijian Kang ◽  
Haiyi Gong ◽  
Da Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Viral Entry ◽  
Digestive System ◽  
Cell Types ◽  
Cell Receptor ◽  
Host Cells ◽  
Target Cells ◽  
Sequencing Data ◽  
Transmembrane Serine Protease ◽  
Coexpression Pattern

ObjectiveSince December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.DesignFive datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.ResultsCell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.ConclusionThis study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

scholarly journals Vitamin D and the Immune System

2021 ◽  
Author(s):  
Vikram Singh Chauhan
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Cell Types ◽  
Surface Proteins ◽  
Target Cells ◽  
B Cell Differentiation ◽  
Regulatory T Lymphocytes ◽  
Factor Α

In the past few decades, various novel actions of vitamin D have been discovered. The mechanism of action of calcitriol or vitamin D is mediated by the Vitamin D receptor (VDR), a subfamily of nuclear receptors, which acts as a transcription factor in the target cells after formation of a heterodimer with the retinoid X receptor (RXR). As the VDR has been found in virtually all cell types, vitamin D exerts multiple actions on different tissues. Vitamin D has important immunomodulatory actions, which includes enhancement of the innate immune system and inhibition of the adaptative immune responses. These actions are associated with an increase in production of interleukin (IL)-4 by T helper (Th)-2 lymphocytes and the up-regulation of regulatory T lymphocytes. Vitamin D can regulate the immune responses in secondary lymphoid organs as well as in target organs through a number of mechanisms. Vitamin D inhibits the expression of APC cytokines, such as interleukin-1 (IL-1), IL-6, IL-12, and tissue necrosis factor- α (TNF-α) and decreases the expression of a set of major histocompatibility complex (MCH) class II cell surface proteins in macrophages. Vitamin D also inhibits B cell differentiation and antibody production. These actions reflect an important role of Vitamin D in balancing the immune system.

scholarly journals Engineering multiple levels of specificity in an RNA viral vector

2020 ◽  
Author(s):  
Xiaojing J. Gao ◽  
Lucy S. Chong ◽  
Michaela H. Ince ◽  
Matthew S. Kim ◽  
Michael B. Elowitz
Keyword(s):  
Viral Vectors ◽  
Viral Vector ◽  
Cell Types ◽  
Model System ◽  
Surface Proteins ◽  
Target Cells ◽  
Specific Cell ◽  
Intracellular Protein ◽  
Cell Surface Proteins ◽  
Multiple Levels

AbstractSynthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal “smart” viral delivery system would enable controlled release of viral vectors from “sender” cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity.

scholarly journals Fas Death Receptor Enhances Endocytic Membrane Traffic Converging into the Golgi Region

2009 ◽  
Vol 20 (2) ◽  
pp. 600-615 ◽  
Author(s):  
Mauro Degli Esposti ◽  
Julien Tour ◽  
Sihem Ouasti ◽  
Saska Ivanova ◽  
Paola Matarrese ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Death Receptor ◽  
Membrane Traffic ◽  
Cell Types ◽  
Systematic Investigation ◽  
Surface Proteins ◽  
Recycling Endosomes ◽  
Receptor Complexes ◽  
Golgi Region ◽  
Fas Signaling

The death receptor Fas/CD95 initiates apoptosis by engaging diverse cellular organelles including endosomes. The link between Fas signaling and membrane traffic has remained unclear, in part because it may differ in diverse cell types. After a systematic investigation of all known pathways of endocytosis, we have clarified that Fas activation opens clathrin-independent portals in mature T cells. These portals drive rapid internalization of surface proteins such as CD59 and depend upon actin-regulating Rho GTPases, especially CDC42. Fas-enhanced membrane traffic invariably produces an accumulation of endocytic membranes around the Golgi apparatus, in which recycling endosomes concentrate. This peri-Golgi polarization has been documented by colocalization analysis of various membrane markers and applies also to active caspases associated with internalized receptor complexes. Hence, T lymphocytes show a diversion in the traffic of endocytic membranes after Fas stimulation that seems to resemble the polarization of membrane traffic after their activation.

scholarly journals SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Dimitris G. Placantonakis ◽  
Maria Aguero-Rosenfeld ◽  
Abdallah Flaifel ◽  
John Colavito ◽  
Kenneth Inglima ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Entry ◽  
Cell Types ◽  
Host Cells ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Neurologic Sequelae ◽  
Show Evidence ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

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