Mycobacterial infection of macrophages results in membrane-permeable phagosomes.

Abstract:

:Cell-mediated immunity is critical for host resistance to tuberculosis. T lymphocytes recognizing antigens presented by the major histocompatibility complex (MHC) class I and class II molecules have been found to be necessary for control of mycobacterial infection. Mice genetically deficient in the generation of MHC class I and class Ia responses are susceptible to mycobacterial infection. Although soluble protein antigens are generally presented by macrophages to T cells through MHC class II molecules, macrophages infected with Mycobacterium tuberculosis or bacille Calmette-Guerin have been shown to facilitate presentation of ovalbumin through the MHC class I presentation pathway via a TAP-dependent mechanism. How mycobacteria, thought to reside within membrane-bound vacuoles, facilitate communication with the cytoplasm and enable MHC class I presentation presents a paradox. By using confocal microscopy to study the localization of fluorescent-tagged dextrans of varying size microinjected intracytoplasmically into macrophages infected with bacille Calmette-Guerin expressing the green fluorescent protein, molecules as large as 70 kilodaltons were shown to gain access to the mycobacterial phagosome. Possible biological consequences of the permeabilization of vacuolar membranes by mycobacteria would be pathogen access to host cell nutrients within the cytoplasm, perhaps contributing to bacterial pathogenesis, and access of microbial antigens to the MHC class I presentation pathway, contributing to host protective immune responses.

authors

Teitelbaum R,Cammer M,Maitland ML,Freitag NE,Condeelis J,Bloom BR

doi

10.1073/pnas.96.26.15190

keywords:

subject

Has Abstract

pub_date

1999-12-21 00:00:00

pages

15190-5

issue

26

eissn

0027-8424

issn

1091-6490

journal_volume

96

pub_type

杂志文章
  • Dissecting Fas signaling with an altered-specificity death-domain mutant: requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation.

    abstract::Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. In many pathologic conditions, ectopic Fas activation mediates tissue destruction. Several proteins that can bind to the cytoplasmic death domain of Fas have been implicated in Fas signal transduction. Here we show that ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.4.1252

    authors: Chang HY,Yang X,Baltimore D

    更新日期:1999-02-16 00:00:00

  • Circular dichroism, molecular modeling, and serology indicate that the structural basis of antigenic variation in foot-and-mouth disease virus is alpha-helix formation.

    abstract::Seven antigenic variants obtained from a single field isolate of foot-and-mouth disease virus, serotype A12, differ only at residues 148 and 153 in the immunodominant loop of viral protein VP1. Synthetic peptides corresponding to the region 141-160 are highly immunogenic. UV circular dichroism shows that (i) in aqueou...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.18.8442

    authors: France LL,Piatti PG,Newman JF,Toth I,Gibbons WA,Brown F

    更新日期:1994-08-30 00:00:00

  • Tyrosine 3-hydroxylase in rat brain and adrenal medulla: hybridization histochemistry and immunohistochemistry combined with retrograde tracing.

    abstract::Rat brain and adrenal gland were analyzed by hybridization histochemistry using an RNA probe complementary to mRNA for tyrosine 3-hydroxylase (TyrOHase; tyrosine 3-monooxygenase, EC 1.14.16.2), by immunohistochemistry using TyrOHase antiserum, and by retrograde tracing using the fluorescent compound Fast blue. Cell bo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.16.6208

    authors: Schalling M,Hökfelt T,Wallace B,Goldstein M,Filer D,Yamin C,Schlesinger DH

    更新日期:1986-08-01 00:00:00

  • Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity.

    abstract::Receptor tyrosine kinases (RTKs) control a multitude of biological processes and are therefore subjected to multiple levels of regulation. Negative feedback is one of the mechanisms that provide an effective means to control RTK-mediated signaling. Sef has recently been identified as a specific antagonist of fibroblas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307952100

    authors: Preger E,Ziv I,Shabtay A,Sher I,Tsang M,Dawid IB,Altuvia Y,Ron D

    更新日期:2004-02-03 00:00:00

  • Early extracellular events in infection of competent Bacillus subtilis by DNA of bacteriophage SP82G.

    abstract::Analysis, by the recovery of specific genetic "markers," of the effects of DNase I, physical shear, and temperature shock on DNA-cell complexes demonstrates that sequential attachment of both ends of bacteriophage SP82G DNA to Bacillus subtilis precedes entry of the DNA molecule into the cell, and that each attachment...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.6.1545

    authors: Williams GL,Green DM

    更新日期:1972-06-01 00:00:00

  • Role of transforming growth factor-alpha in von Hippel--Lindau (VHL)(-/-) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis.

    abstract::Mutations of the VHL tumor suppressor gene occur in patients with VHL disease and in the majority of sporadic clear cell renal carcinomas (VHL(-/-) RCC). Loss of VHL protein function is associated with constitutive expression of mRNAs encoding hypoxia-inducible proteins, such as vascular endothelial growth factor. Ove...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.031587498

    authors: de Paulsen N,Brychzy A,Fournier MC,Klausner RD,Gnarra JR,Pause A,Lee S

    更新日期:2001-02-13 00:00:00

  • Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

    abstract::Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1512570112

    authors: Gao X,Zhao Y,Stemmer-Rachamimov AO,Liu H,Huang P,Chin S,Selig MK,Plotkin SR,Jain RK,Xu L

    更新日期:2015-11-24 00:00:00

  • Futile transmembrane NH4(+) cycling: a cellular hypothesis to explain ammonium toxicity in plants.

    abstract::Most higher plants develop severe toxicity symptoms when grown on ammonium (NH(4)(+)) as the sole nitrogen source. Recently, NH(4)(+) toxicity has been implicated as a cause of forest decline and even species extinction. Although mechanisms underlying NH(4)(+) toxicity have been extensively sought, the primary events ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.061034698

    authors: Britto DT,Siddiqi MY,Glass AD,Kronzucker HJ

    更新日期:2001-03-27 00:00:00

  • Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex.

    abstract::Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on neurogenesis and neuronal survival in humans. However, most studies on DHEA have been performed in rodents, and there is little direct evidence for biological effects on the human nervous system. Furthermore, the mechanism of its action is unkno...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307325101

    authors: Suzuki M,Wright LS,Marwah P,Lardy HA,Svendsen CN

    更新日期:2004-03-02 00:00:00

  • Additivity of mutant effects assessed by binomial mutagenesis.

    abstract::Eleven amino acid positions in the helix-turn-helix of lambda repressor have been mutagenized by using a combinatorial method in which alanine is substituted at each position with a probability of 0.5. Approximately 25% of the 2048 proteins in the resulting binomial library are active, including some variants with as ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.9.4246

    authors: Gregoret LM,Sauer RT

    更新日期:1993-05-01 00:00:00

  • Allosteric modulation of alternatively spliced Ca2+-activated Cl- channels TMEM16A by PI(4,5)P2 and CaMKII.

    abstract::Transmembrane 16A (TMEM16A, anoctamin1), 1 of 10 TMEM16 family proteins, is a Cl- channel activated by intracellular Ca2+ and membrane voltage. This channel is also regulated by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. We find that two splice variants of TMEM16A show different sensi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2014520117

    authors: Ko W,Jung SR,Kim KW,Yeon JH,Park CG,Nam JH,Hille B,Suh BC

    更新日期:2020-12-01 00:00:00

  • Structure-function relationships of the yeast fatty acid synthase: negative-stain, cryo-electron microscopy, and image analysis studies of the end views of the structure.

    abstract::The yeast fatty acid synthase (M(r) = 2.5 x 10(6)) is organized in an alpha 6 beta 6 complex. In these studies, the synthase structure has been examined by negative-stain and cryo-electron microscopy. Side and end views of the structure indicate that the molecule, shaped similar to a prolate ellipsoid, has a high-dens...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.14.6585

    authors: Stoops JK,Kolodziej SJ,Schroeter JP,Bretaudiere JP,Wakil SJ

    更新日期:1992-07-15 00:00:00

  • Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation.

    abstract::The circadian clock in eukaryotes controls transcriptional and posttranscriptional events, including regulation of the levels and phosphorylation state of translation factors. However, the mechanisms underlying clock control of translation initiation, and the impact of this potential regulation on rhythmic protein syn...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1918459117

    authors: Karki S,Castillo K,Ding Z,Kerr O,Lamb TM,Wu C,Sachs MS,Bell-Pedersen D

    更新日期:2020-05-19 00:00:00

  • Tumor promoters cause a rapid and reversible inhibition of the formation and maintenance of electrical cell coupling in culture.

    abstract::The effect of tumor promoters on electrical coupling between human FL cells was investigated with a microelectrode technique. When a low concentration (100 ng/ml) of 12-O-tetradecanoylphorbol 13-acetate (TPA) was added to culture medium, only 6% of the cells showed electrical coupling after 5 hr, whereas in control me...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.9.5628

    authors: Enomoto T,Sasaki Y,Shiba Y,Kanno Y,Yamasaki H

    更新日期:1981-09-01 00:00:00

  • Cluster-like coordinates in supersymmetric quantum field theory.

    abstract::Recently it has become apparent that N = 2 supersymmetric quantum field theory has something to do with cluster algebras. I review one aspect of the connection: supersymmetric quantum field theories have associated hyperkähler moduli spaces, and these moduli spaces carry a structure that looks like an extension of the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1313073111

    authors: Neitzke A

    更新日期:2014-07-08 00:00:00

  • Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.

    abstract::We report the isolation and sequencing of cDNAs encoding two human glutamate decarboxylases (GADs; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), GAD65 and GAD67. Human GAD65 cDNA encodes a Mr 65,000 polypeptide, with 585 amino acid residues, whereas human GAD67 encodes a Mr 67,000 polypeptide, with 594 amino acid residue...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.6.2115

    authors: Bu DF,Erlander MG,Hitz BC,Tillakaratne NJ,Kaufman DL,Wagner-McPherson CB,Evans GA,Tobin AJ

    更新日期:1992-03-15 00:00:00

  • Comparison of somatic mutation in a transgenic versus host locus.

    abstract::Somatic mutations can now be quantified in almost any cell type in mice carrying bacterial genes in a lambda phage shuttle vector. Mutations induced in vivo are detectable ex vivo, after packaging host-cell DNA into phage that are grown on suitable bacteria. However, the transgenic DNA differs from many host loci in s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.22.10681

    authors: Tao KS,Urlando C,Heddle JA

    更新日期:1993-11-15 00:00:00

  • Independent circuits in the basal ganglia for the evaluation and selection of actions.

    abstract::The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314815110

    authors: Stephenson-Jones M,Kardamakis AA,Robertson B,Grillner S

    更新日期:2013-09-17 00:00:00

  • Heterogeneous activation thresholds to cytokines in genetically distinct endothelial cells: evidence for diverse transcriptional responses.

    abstract::It is well accepted that the induction of endothelial cell (EC) adhesion molecules is a critical component in acute inflammatory responses as well as allogeneic interactions in vascularized allografts and, possibly, atherogenesis. The "inflammatory triad" of interleukin 1 (IL-1), tumor necrosis factor, and lipopolysac...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.9.3994

    authors: Bender JR,Sadeghi MM,Watson C,Pfau S,Pardi R

    更新日期:1994-04-26 00:00:00

  • Tracking lineages of single cells in lines using a microfluidic device.

    abstract::Cells within a genetically identical population exhibit phenotypic variation that in some cases can persist across multiple generations. However, information about the temporal variation and familial dependence of protein levels remains hidden when studying the population as an ensemble. To correlate phenotypes with t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903163106

    authors: Rowat AC,Bird JC,Agresti JJ,Rando OJ,Weitz DA

    更新日期:2009-10-27 00:00:00

  • Titanospirillum velox: a huge, speedy, sulfur-storing spirillum from Ebro Delta microbial mats.

    abstract::A long (20-30 micrometer), wide (3-5 micrometer) microbial-mat bacterium from the Ebro Delta (Tarragona, Spain) was grown in mixed culture and videographed live. Intracellular elemental sulfur globules and unique cell termini were observed in scanning-electron-microprobe and transmission-electron micrographs. A polar ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.20.11584

    authors: Guerrero R,Haselton A,Solé M,Wier A,Margulis L

    更新日期:1999-09-28 00:00:00

  • Apparent failure of the Born-Oppenheimer static surface model for vibrational excitation of molecular hydrogen on copper.

    abstract::The accuracy of dynamical models for reactive scattering of molecular hydrogen, H(2), from metal surfaces is relevant to the validation of first principles electronic structure methods for molecules interacting with metal surfaces. The ability to validate such methods is important to progress in modeling heterogeneous...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1001098107

    authors: Kroes GJ,Díaz C,Pijper E,Olsen RA,Auerbach DJ

    更新日期:2010-12-07 00:00:00

  • Molecular cloning of beta 3 subunit, a third form of the G protein beta-subunit polypeptide.

    abstract::The signal-transducing guanine nucleotide-binding regulatory (G) proteins are heterotrimers composed of three subunits--alpha, beta, and gamma. Although multiple distinctive forms of the alpha subunit have been described, only two forms of the beta subunits of the G proteins have been identified. To investigate furthe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.6.2329

    authors: Levine MA,Smallwood PM,Moen PT Jr,Helman LJ,Ahn TG

    更新日期:1990-03-01 00:00:00

  • Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles.

    abstract::The structural and functional organization of the cell nucleus has been investigated using three-dimensional reconstruction, immunoelectron microscopy, and high-resolution in situ autoradiography. Nuclear regions enriched in small nuclear ribonucleoprotein particles (snRNPs) form a reticular network within the nucleop...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.1.147

    authors: Spector DL

    更新日期:1990-01-01 00:00:00

  • A single-stranded DNA binding protein binds the origin of replication of the duplex kinetoplast DNA.

    abstract::Replication of the kinetoplast DNA (kDNA) minicircle of trypanosomatids initiates at a conserved 12-nt sequence, 5'-GGGGTTGGTGTA-3', termed the universal minicircle sequence (UMS). A sequence-specific single-stranded DNA-binding protein from Crithidia fasciculata binds the heavy strand of the 12-mer UMS. Whereas this ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.23.10511

    authors: Avrahami D,Tzfati Y,Shlomai J

    更新日期:1995-11-07 00:00:00

  • B cells are critical for autoimmune pathology in Scurfy mice.

    abstract::Impaired regulatory T-cell function results in a severe chronic autoimmune disease affecting multiple organs in Scurfy mice and humans with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Previous studies have shown that T helper cells but not cytotoxic T cells are critical for the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1313547110

    authors: Aschermann S,Lehmann CH,Mihai S,Schett G,Dudziak D,Nimmerjahn F

    更新日期:2013-11-19 00:00:00

  • Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor.

    abstract::In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of a network of genes encoding erythropoietin, vascular endothelial growth factor, and several glycolytic enzymes. HIF-1 consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim) proteins, HIF-1alpha and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.11.5667

    authors: Kallio PJ,Pongratz I,Gradin K,McGuire J,Poellinger L

    更新日期:1997-05-27 00:00:00

  • Levinthal's paradox.

    abstract::Levinthal's paradox is that finding the native folded state of a protein by a random search among all possible configurations can take an enormously long time. Yet proteins can fold in seconds or less. Mathematical analysis of a simple model shows that a small and physically reasonable energy bias against locally unfa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.1.20

    authors: Zwanzig R,Szabo A,Bagchi B

    更新日期:1992-01-01 00:00:00

  • Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy.

    abstract::Strategies to treat cancer have focused primarily on the killing of tumor cells. Here, we describe a differential stress resistance (DSR) method that focuses instead on protecting the organism but not cancer cells against chemotherapy. Short-term starved S. cerevisiae or cells lacking proto-oncogene homologs were up t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0708100105

    authors: Raffaghello L,Lee C,Safdie FM,Wei M,Madia F,Bianchi G,Longo VD

    更新日期:2008-06-17 00:00:00

  • Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways.

    abstract::Some tumor cell lines secrete high concentrations of TGFbeta or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFbeta activates NFkappaB, and IL-1beta activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0700118104

    authors: Lu T,Tian L,Han Y,Vogelbaum M,Stark GR

    更新日期:2007-03-13 00:00:00