B7-H1 blockade increases survival of dysfunctional CD8(+) T cells and confers protection against Leishmania donovani infections.

Abstract:

:Experimental visceral leishmaniasis (VL) represents an exquisite model to study CD8(+) T cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and CD8(+) T cells are required for the development of protective immunity. However, antigen-specific CD8(+) T cell responses in VL have so far not been studied, due to the absence of any defined Leishmania-specific CD8(+) T cell epitopes. In this study, transgenic Leishmania donovani parasites expressing ovalbumin were used to characterize the development, function, and fate of Leishmania-specific CD8(+) T cell responses. Here we show that L. donovani parasites evade CD8(+) T cell responses by limiting their expansion and inducing functional exhaustion and cell death. Dysfunctional CD8(+) T cells could be partially rescued by in vivo B7-H1 blockade, which increased CD8(+) T cell survival but failed to restore cytokine production. Nevertheless, B7-H1 blockade significantly reduced the splenic parasite burden. These findings could be exploited for the design of new strategies for immunotherapeutic interventions against VL.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Joshi T,Rodriguez S,Perovic V,Cockburn IA,Stäger S

doi

10.1371/journal.ppat.1000431

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

e1000431

issue

5

eissn

1553-7366

issn

1553-7374

journal_volume

5

pub_type

杂志文章
  • The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

    abstract::In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic el...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,随机对照试验

    doi:10.1371/journal.ppat.1006966

    authors: Azarian T,Grant LR,Arnold BJ,Hammitt LL,Reid R,Santosham M,Weatherholtz R,Goklish N,Thompson CM,Bentley SD,O'Brien KL,Hanage WP,Lipsitch M

    更新日期:2018-04-04 00:00:00

  • Inflammation fuels colicin Ib-dependent competition of Salmonella serovar Typhimurium and E. coli in enterobacterial blooms.

    abstract::The host's immune system plays a key role in modulating growth of pathogens and the intestinal microbiota in the gut. In particular, inflammatory bowel disorders and pathogen infections induce shifts of the resident commensal microbiota which can result in overgrowth of Enterobacteriaceae ("inflammation-inflicted bloo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003844

    authors: Nedialkova LP,Denzler R,Koeppel MB,Diehl M,Ring D,Wille T,Gerlach RG,Stecher B

    更新日期:2014-01-01 00:00:00

  • CdtR Regulates TcdA and TcdB Production in Clostridium difficile.

    abstract::Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B) and TcdA (toxin A) in the Pathogenicity ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005758

    authors: Lyon SA,Hutton ML,Rood JI,Cheung JK,Lyras D

    更新日期:2016-07-14 00:00:00

  • Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport.

    abstract::Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellu...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006603

    authors: Guichard A,Jain P,Moayeri M,Schwartz R,Chin S,Zhu L,Cruz-Moreno B,Liu JZ,Aguilar B,Hollands A,Leppla SH,Nizet V,Bier E

    更新日期:2017-09-25 00:00:00

  • The plant actin cytoskeleton responds to signals from microbe-associated molecular patterns.

    abstract::Plants are constantly exposed to a large and diverse array of microbes; however, most plants are immune to the majority of potential invaders and susceptible to only a small subset of pathogens. The cytoskeleton comprises a dynamic intracellular framework that responds rapidly to biotic stresses and supports numerous ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003290

    authors: Henty-Ridilla JL,Shimono M,Li J,Chang JH,Day B,Staiger CJ

    更新日期:2013-01-01 00:00:00

  • Cooperation between Epstein-Barr virus immune evasion proteins spreads protection from CD8+ T cell recognition across all three phases of the lytic cycle.

    abstract::CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that t...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004322

    authors: Quinn LL,Zuo J,Abbott RJ,Shannon-Lowe C,Tierney RJ,Hislop AD,Rowe M

    更新日期:2014-08-21 00:00:00

  • Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    abstract::Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been w...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004689

    authors: Creek DJ,Mazet M,Achcar F,Anderson J,Kim DH,Kamour R,Morand P,Millerioux Y,Biran M,Kerkhoven EJ,Chokkathukalam A,Weidt SK,Burgess KE,Breitling R,Watson DG,Bringaud F,Barrett MP

    更新日期:2015-03-16 00:00:00

  • The risk of sustained sexual transmission of Zika is underestimated.

    abstract::Pathogens often follow more than one transmission route during outbreaks-from needle sharing plus sexual transmission of HIV to small droplet aerosol plus fomite transmission of influenza. Thus, controlling an infectious disease outbreak often requires characterizing the risk associated with multiple mechanisms of tra...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006633

    authors: Allard A,Althouse BM,Hébert-Dufresne L,Scarpino SV

    更新日期:2017-09-21 00:00:00

  • The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function.

    abstract::Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphyloco...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006461

    authors: Tuffs SW,James DBA,Bestebroer J,Richards AC,Goncheva MI,O'Shea M,Wee BA,Seo KS,Schlievert PM,Lengeling A,van Strijp JA,Torres VJ,Fitzgerald JR

    更新日期:2017-09-07 00:00:00

  • Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection.

    abstract::Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of t...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003687

    authors: Gillet NA,Gutiérrez G,Rodriguez SM,de Brogniez A,Renotte N,Alvarez I,Trono K,Willems L

    更新日期:2013-01-01 00:00:00

  • Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

    abstract::The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolut...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001195

    authors: Sabin C,Corti D,Buzon V,Seaman MS,Lutje Hulsik D,Hinz A,Vanzetta F,Agatic G,Silacci C,Mainetti L,Scarlatti G,Sallusto F,Weiss R,Lanzavecchia A,Weissenhorn W

    更新日期:2010-11-18 00:00:00

  • Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

    abstract::Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000429

    authors: Jia B,Serra-Moreno R,Neidermyer W,Rahmberg A,Mackey J,Fofana IB,Johnson WE,Westmoreland S,Evans DT

    更新日期:2009-05-01 00:00:00

  • Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles.

    abstract::Transmission of prions between species is limited by the "species barrier," which hampers a full characterization of human prion strains in the mouse model. We report that the efficiency of primary transmission of prions from Creutzfeldt-Jakob disease patients to a wild rodent species, the bank vole (Clethrionomys gla...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0020012

    authors: Nonno R,Di Bari MA,Cardone F,Vaccari G,Fazzi P,Dell'Omo G,Cartoni C,Ingrosso L,Boyle A,Galeno R,Sbriccoli M,Lipp HP,Bruce M,Pocchiari M,Agrimi U

    更新日期:2006-02-01 00:00:00

  • The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

    abstract::The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protei...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005835

    authors: Vázquez-Fernández E,Vos MR,Afanasyev P,Cebey L,Sevillano AM,Vidal E,Rosa I,Renault L,Ramos A,Peters PJ,Fernández JJ,van Heel M,Young HS,Requena JR,Wille H

    更新日期:2016-09-08 00:00:00

  • Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells.

    abstract::Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006732

    authors: Treat BR,Bidula SM,Ramachandran S,St Leger AJ,Hendricks RL,Kinchington PR

    更新日期:2017-12-04 00:00:00

  • AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans.

    abstract::The role of Activation-Induced Cytidine Deaminase (AID) in somatic hypermutation and polyclonal antibody affinity maturation has not been shown for polyclonal responses in humans. We investigated whether AID induction in human B cells following H1N1pdm09 vaccination correlated with in-vivo antibody affinity maturation...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002920

    authors: Khurana S,Frasca D,Blomberg B,Golding H

    更新日期:2012-09-01 00:00:00

  • Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

    abstract::Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This va...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005614

    authors: Price DN,Kusewitt DF,Lino CA,McBride AA,Muttil P

    更新日期:2016-05-06 00:00:00

  • Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles.

    abstract::The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the caps...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006929

    authors: Smith JK,Agbandje-McKenna M

    更新日期:2018-05-03 00:00:00

  • Mannose binding lectin is required for alphavirus-induced arthritis/myositis.

    abstract::Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within th...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002586

    authors: Gunn BM,Morrison TE,Whitmore AC,Blevins LK,Hueston L,Fraser RJ,Herrero LJ,Ramirez R,Smith PN,Mahalingam S,Heise MT

    更新日期:2012-01-01 00:00:00

  • Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal cells.

    abstract::The intestine is a common site for invasion by intracellular pathogens, but little is known about how pathogens restructure and exit intestinal cells in vivo. The natural microsporidian parasite N. parisii invades intestinal cells of the nematode C. elegans, progresses through its life cycle, and then exits cells in a...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002227

    authors: Estes KA,Szumowski SC,Troemel ER

    更新日期:2011-09-01 00:00:00

  • Divergent bornaviruses from Australian carpet pythons with neurological disease date the origin of extant Bornaviridae prior to the end-Cretaceous extinction.

    abstract::Tissue samples from Australian carpet pythons (Morelia spilota) with neurological disease were screened for viruses using next-generation sequencing. Coding complete genomes of two bornaviruses were identified with the gene order 3'-N-X-P-G-M-L, representing a transposition of the G and M genes compared to other borna...

    journal_title:PLoS pathogens

    pub_type: 历史文章,杂志文章

    doi:10.1371/journal.ppat.1006881

    authors: Hyndman TH,Shilton CM,Stenglein MD,Wellehan JFX Jr

    更新日期:2018-02-20 00:00:00

  • Convergent use of RhoGAP toxins by eukaryotic parasites and bacterial pathogens.

    abstract::Inactivation of host Rho GTPases is a widespread strategy employed by bacterial pathogens to manipulate mammalian cellular functions and avoid immune defenses. Some bacterial toxins mimic eukaryotic Rho GTPase-activating proteins (GAPs) to inactivate mammalian GTPases, probably as a result of evolutionary convergence....

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030203

    authors: Colinet D,Schmitz A,Depoix D,Crochard D,Poirié M

    更新日期:2007-12-28 00:00:00

  • Listeria monocytogenes cytoplasmic entry induces fetal wastage by disrupting maternal Foxp3+ regulatory T cell-sustained fetal tolerance.

    abstract::Although the intracellular bacterium Listeria monocytogenes has an established predilection for disseminated infection during pregnancy that often results in spontaneous abortion or stillbirth, the specific host-pathogen interaction that dictates these disastrous complications remain incompletely defined. Herein, we d...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002873

    authors: Rowe JH,Ertelt JM,Xin L,Way SS

    更新日期:2012-01-01 00:00:00

  • Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    abstract::In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000362

    authors: Rittner HL,Hackel D,Voigt P,Mousa S,Stolz A,Labuz D,Schäfer M,Schaefer M,Stein C,Brack A

    更新日期:2009-04-01 00:00:00

  • The AraC Negative Regulator family modulates the activity of histone-like proteins in pathogenic bacteria.

    abstract::The AraC Negative Regulators (ANR) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., and pathogenic E. coli strains. We have previously reported broad effects of...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006545

    authors: Santiago AE,Yan MB,Hazen TH,Sauder B,Meza-Segura M,Rasko DA,Kendall MM,Ruiz-Perez F,Nataro JP

    更新日期:2017-08-14 00:00:00

  • The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.

    abstract::PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002067

    authors: Varga ZT,Ramos I,Hai R,Schmolke M,García-Sastre A,Fernandez-Sesma A,Palese P

    更新日期:2011-06-01 00:00:00

  • Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus.

    abstract::The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000141

    authors: Saeed MF,Kolokoltsov AA,Freiberg AN,Holbrook MR,Davey RA

    更新日期:2008-08-29 00:00:00

  • Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress.

    abstract::Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006132

    authors: Liang J,Sagum CA,Bedford MT,Sidhu SS,Sudol M,Han Z,Harty RN

    更新日期:2017-01-11 00:00:00

  • Strain-specific differences in the genetic control of two closely related mycobacteria.

    abstract::The host response to mycobacterial infection depends on host and pathogen genetic factors. Recent studies in human populations suggest a strain specific genetic control of tuberculosis. To test for mycobacterial-strain specific genetic control of susceptibility to infection under highly controlled experimental conditi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001169

    authors: Di Pietrantonio T,Hernandez C,Girard M,Verville A,Orlova M,Belley A,Behr MA,Loredo-Osti JC,Schurr E

    更新日期:2010-10-28 00:00:00

  • Horizontal versus familial transmission of Helicobacter pylori.

    abstract::Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000180

    authors: Schwarz S,Morelli G,Kusecek B,Manica A,Balloux F,Owen RJ,Graham DY,van der Merwe S,Achtman M,Suerbaum S

    更新日期:2008-10-01 00:00:00