TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

Abstract:

:HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Chew GM,Fujita T,Webb GM,Burwitz BJ,Wu HL,Reed JS,Hammond KB,Clayton KL,Ishii N,Abdel-Mohsen M,Liegler T,Mitchell BI,Hecht FM,Ostrowski M,Shikuma CM,Hansen SG,Maurer M,Korman AJ,Deeks SG,Sacha JB,Ndhlovu LC

doi

10.1371/journal.ppat.1005349

subject

Has Abstract

pub_date

2016-01-07 00:00:00

pages

e1005349

issue

1

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-15-01706

journal_volume

12

pub_type

杂志文章
  • Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.

    abstract::Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an activ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005045

    authors: Zühlsdorf M,Werten S,Klupp BG,Palm GJ,Mettenleiter TC,Hinrichs W

    更新日期:2015-07-10 00:00:00

  • Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger.

    abstract::Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005373

    authors: Markosyan RM,Miao C,Zheng YM,Melikyan GB,Liu SL,Cohen FS

    更新日期:2016-01-05 00:00:00

  • Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    abstract::Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whet...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030123

    authors: Robbins SH,Bessou G,Cornillon A,Zucchini N,Rupp B,Ruzsics Z,Sacher T,Tomasello E,Vivier E,Koszinowski UH,Dalod M

    更新日期:2007-08-24 00:00:00

  • Prion shedding from olfactory neurons into nasal secretions.

    abstract::This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000837

    authors: Bessen RA,Shearin H,Martinka S,Boharski R,Lowe D,Wilham JM,Caughey B,Wiley JA

    更新日期:2010-04-15 00:00:00

  • Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and required for varicella-zoster virus pathogenesis in skin.

    abstract::Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002157

    authors: Wang L,Oliver SL,Sommer M,Rajamani J,Reichelt M,Arvin AM

    更新日期:2011-08-01 00:00:00

  • Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins.

    abstract::Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章

    doi:10.1371/journal.ppat.1003653

    authors: Hazenbos WL,Kajihara KK,Vandlen R,Morisaki JH,Lehar SM,Kwakkenbos MJ,Beaumont T,Bakker AQ,Phung Q,Swem LR,Ramakrishnan S,Kim J,Xu M,Shah IM,Diep BA,Sai T,Sebrell A,Khalfin Y,Oh A,Koth C,Lin SJ,Lee BC,Strandh M

    更新日期:2013-01-01 00:00:00

  • Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.

    abstract::Interferons (IFNs) are a group of cytokines with a well-established antiviral function. They can be induced by viral infection, are secreted and bind to specific receptors on the same or neighbouring cells to activate the expression of hundreds of IFN stimulated genes (ISGs) with antiviral function. Type I IFN has bee...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003773

    authors: Crotta S,Davidson S,Mahlakoiv T,Desmet CJ,Buckwalter MR,Albert ML,Staeheli P,Wack A

    更新日期:2013-01-01 00:00:00

  • AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica.

    abstract::The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006882

    authors: Nakada-Tsukui K,Sekizuka T,Sato-Ebine E,Escueta-de Cadiz A,Ji DD,Tomii K,Kuroda M,Nozaki T

    更新日期:2018-03-19 00:00:00

  • Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

    abstract::KSHV is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentricCastleman's disease (MCD). The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regula...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002884

    authors: Haecker I,Gay LA,Yang Y,Hu J,Morse AM,McIntyre LM,Renne R

    更新日期:2012-01-01 00:00:00

  • Elucidation of the RamA regulon in Klebsiella pneumoniae reveals a role in LPS regulation.

    abstract::Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004627

    authors: De Majumdar S,Yu J,Fookes M,McAteer SP,Llobet E,Finn S,Spence S,Monahan A,Monaghan A,Kissenpfennig A,Ingram RJ,Bengoechea J,Gally DL,Fanning S,Elborn JS,Schneiders T

    更新日期:2015-01-29 00:00:00

  • A compact viral processing proteinase/ubiquitin hydrolase from the OTU family.

    abstract::Turnip yellow mosaic virus (TYMV)--a member of the alphavirus-like supergroup of viruses--serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (P...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003560

    authors: Lombardi C,Ayach M,Beaurepaire L,Chenon M,Andreani J,Guerois R,Jupin I,Bressanelli S

    更新日期:2013-08-01 00:00:00

  • Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C.

    abstract::The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to "bumpy" surfaced morphology when the temperature is switched from 29°C at 37°...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007996

    authors: Lim XN,Shan C,Marzinek JK,Dong H,Ng TS,Ooi JSG,Fibriansah G,Wang J,Verma CS,Bond PJ,Shi PY,Lok SM

    更新日期:2019-09-19 00:00:00

  • Inhibition of IL-10 production by maternal antibodies against Group B Streptococcus GAPDH confers immunity to offspring by favoring neutrophil recruitment.

    abstract::Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleuk...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002363

    authors: Madureira P,Andrade EB,Gama B,Oliveira L,Moreira S,Ribeiro A,Correia-Neves M,Trieu-Cuot P,Vilanova M,Ferreira P

    更新日期:2011-11-01 00:00:00

  • Francisella tularensis IglG Belongs to a Novel Family of PAAR-Like T6SS Proteins and Harbors a Unique N-terminal Extension Required for Virulence.

    abstract::The virulence of Francisella tularensis, the etiological agent of tularemia, relies on an atypical type VI secretion system (T6SS) encoded by a genomic island termed the Francisella Pathogenicity Island (FPI). While the importance of the FPI in F. tularensis virulence is clearly established, the precise role of most o...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005821

    authors: Rigard M,Bröms JE,Mosnier A,Hologne M,Martin A,Lindgren L,Punginelli C,Lays C,Walker O,Charbit A,Telouk P,Conlan W,Terradot L,Sjöstedt A,Henry T

    更新日期:2016-09-07 00:00:00

  • Structural insights into viral determinants of nematode mediated Grapevine fanleaf virus transmission.

    abstract::Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV), a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP),...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002034

    authors: Schellenberger P,Sauter C,Lorber B,Bron P,Trapani S,Bergdoll M,Marmonier A,Schmitt-Keichinger C,Lemaire O,Demangeat G,Ritzenthaler C

    更新日期:2011-05-01 00:00:00

  • Mechanism of HIV-1 virion entrapment by tetherin.

    abstract::Tetherin, an interferon-inducible membrane protein, inhibits the release of nascent enveloped viral particles from the surface of infected cells. However, the mechanisms underlying virion retention have not yet been fully delineated. Here, we employ biochemical assays and engineered tetherin proteins to demonstrate co...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003483

    authors: Venkatesh S,Bieniasz PD

    更新日期:2013-01-01 00:00:00

  • Wolbachia symbiont infections induce strong cytoplasmic incompatibility in the tsetse fly Glossina morsitans.

    abstract::Tsetse flies are vectors of the protozoan parasite African trypanosomes, which cause sleeping sickness disease in humans and nagana in livestock. Although there are no effective vaccines and efficacious drugs against this parasite, vector reduction methods have been successful in curbing the disease, especially for na...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002415

    authors: Alam U,Medlock J,Brelsfoard C,Pais R,Lohs C,Balmand S,Carnogursky J,Heddi A,Takac P,Galvani A,Aksoy S

    更新日期:2011-12-01 00:00:00

  • MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference.

    abstract::In addition to modulating the function and stability of cellular mRNAs, microRNAs can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. To elucidate the mechanisms underlying microRNA-mediated an...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000820

    authors: Kelly EJ,Hadac EM,Cullen BR,Russell SJ

    更新日期:2010-03-19 00:00:00

  • Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse.

    abstract::Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, including sepsis and necrotiz...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005732

    authors: Chella Krishnan K,Mukundan S,Alagarsamy J,Hur J,Nookala S,Siemens N,Svensson M,Hyldegaard O,Norrby-Teglund A,Kotb M

    更新日期:2016-07-11 00:00:00

  • Experimental evolution of Legionella pneumophila in mouse macrophages leads to strains with altered determinants of environmental survival.

    abstract::The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose a model in which cycling through multiple protozoan hosts in the environment holds L. pneumophila in a state of evolutionary stasis as a broad host-range pathogen. Using an experimen...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002731

    authors: Ensminger AW,Yassin Y,Miron A,Isberg RR

    更新日期:2012-01-01 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

  • Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system.

    abstract::Many bacterial pathogens and symbionts use type III secretion machines to interact with their hosts by injecting bacterial effector proteins into host target cells. A central component of this complex machine is the cytoplasmic sorting platform, which orchestrates the engagement and preparation of type III secreted pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007565

    authors: Lara-Tejero M,Qin Z,Hu B,Butan C,Liu J,Galán JE

    更新日期:2019-01-22 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

  • Viral protein inhibits RISC activity by argonaute binding through conserved WG/GW motifs.

    abstract::RNA silencing is an evolutionarily conserved sequence-specific gene-inactivation system that also functions as an antiviral mechanism in higher plants and insects. To overcome antiviral RNA silencing, viruses express silencing-suppressor proteins. These viral proteins can target one or more key points in the silencing...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000996

    authors: Giner A,Lakatos L,García-Chapa M,López-Moya JJ,Burgyán J

    更新日期:2010-07-15 00:00:00

  • Genome-scale multilocus microsatellite typing of Trypanosoma cruzi discrete typing unit I reveals phylogeographic structure and specific genotypes linked to human infection.

    abstract::Trypanosoma cruzi is the most important parasitic infection in Latin America and is also genetically highly diverse, with at least six discrete typing units (DTUs) reported: Tc I, IIa, IIb, IIc, IId, and IIe. However, the current six-genotype classification is likely to be a poor reflection of the total genetic divers...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000410

    authors: Llewellyn MS,Miles MA,Carrasco HJ,Lewis MD,Yeo M,Vargas J,Torrico F,Diosque P,Valente V,Valente SA,Gaunt MW

    更新日期:2009-05-01 00:00:00

  • The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.

    abstract::The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000447

    authors: Hovius JW,Bijlsma MF,van der Windt GJ,Wiersinga WJ,Boukens BJ,Coumou J,Oei A,de Beer R,de Vos AF,van 't Veer C,van Dam AP,Wang P,Fikrig E,Levi MM,Roelofs JJ,van der Poll T

    更新日期:2009-05-01 00:00:00

  • Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases.

    abstract::The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at p...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004180

    authors: Brown KM,Suvorova E,Farrell A,McLain A,Dittmar A,Wiley GB,Marth G,Gaffney PM,Gubbels MJ,White M,Blader IJ

    更新日期:2014-06-12 00:00:00

  • A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function.

    abstract:TRIAL REGISTRATION:ClinicalTrials.gov Clinical Trial NCT00594880. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006806

    authors: Chitre AS,Kattah MG,Rosli YY,Pao M,Deswal M,Deeks SG,Hunt PW,Abdel-Mohsen M,Montaner LJ,Kim CC,Ma A,Somsouk M,McCune JM

    更新日期:2018-03-05 00:00:00

  • A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    abstract::From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005074

    authors: de Groof A,Guelen L,Deijs M,van der Wal Y,Miyata M,Ng KS,van Grinsven L,Simmelink B,Biermann Y,Grisez L,van Lent J,de Ronde A,Chang SF,Schrier C,van der Hoek L

    更新日期:2015-08-07 00:00:00

  • Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

    abstract::The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs,...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001266

    authors: Reichelt M,Wang L,Sommer M,Perrino J,Nour AM,Sen N,Baiker A,Zerboni L,Arvin AM

    更新日期:2011-02-03 00:00:00