scholarly journals Bacterial inhibition of CD8+ T-cells mediated cell death promotes neuroinvasion and within-host persistence

2021 ◽  
Author(s):  
Marc Lecuit ◽  
Claire Maudet ◽  
Marouane Kheloufi ◽  
Sylvain Levallois ◽  
Julien Gaillard ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cell Death ◽  
Nervous System ◽  
Cd8 T Cells ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Central Nervous System Infections ◽  
Humanized Mouse Model ◽  
The Brain

Abstract Central nervous system infections are amongst the most severe, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections. While immunosuppression is a well-established host risk factor for neurolisteriosis, little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains inoculated in a humanized mouse model of infection, and we show that the bacterial protein InlB protects infected monocytes from CD8+ T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.

scholarly journals Bacterial inhibition of CD8+ T-cells mediated cell death promotes neuroinvasion and within-host persistence

2020 ◽  
Author(s):  
Claire Maudet ◽  
Marouane Kheloufi ◽  
Sylvain Levallois ◽  
Julien Gaillard ◽  
Lei Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cell Death ◽  
Nervous System ◽  
Virulence Gene ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Central Nervous System Infections ◽  
Humanized Mouse Model ◽  
The Brain

AbstractCentral nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6 inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+ T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.

scholarly journals Migration of CD8+T Cells into the Central Nervous System Gives Rise to Highly Potent Anti-HIV CD4dimCD8brightT Cells in a Wnt Signaling–Dependent Manner

2015 ◽  
Vol 196 (1) ◽  
pp. 317-327 ◽  
Author(s):  
Maureen H. Richards ◽  
Srinivas D. Narasipura ◽  
Melanie S. Seaton ◽  
Victoria Lutgen ◽  
Lena Al-Harthi
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Wnt Signaling ◽  
Cd8 T Cells ◽  
Dependent Manner ◽  
The Central Nervous System ◽  
Anti Hiv

scholarly journals To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 842 ◽  
Author(s):  
Taryn E. Mockus ◽  
Heather M. Ren ◽  
Shwetank ◽  
Aron E. Lukacher
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Memory Cd8 T Cells ◽  
The Central Nervous System ◽  
Cd8 T Cell Memory ◽  
Maintenance Requirements ◽  
The Brain

CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bTRM). CD8 bTRM are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bTRM have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bTRM and discuss their roles in controlling viral infections of the brain.

scholarly journals Highly Activated CD8+T Cells in the Brain Correlate with Early Central Nervous System Dysfunction in Simian Immunodeficiency Virus Infection

2001 ◽  
Vol 167 (9) ◽  
pp. 5429-5438 ◽  
Author(s):  
Maria Cecilia Garibaldi Marcondes ◽  
E. M. E. Burudi ◽  
Salvador Huitron-Resendiz ◽  
Manuel Sanchez-Alavez ◽  
Debbie Watry ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Cd8 T Cells ◽  
Simian Immunodeficiency Virus Infection ◽  
Central Nervous System Dysfunction ◽  
Immunodeficiency Virus ◽  
The Brain

scholarly journals Immune Autoregulatory CD8 T Cells Require IFN-γ Responsiveness to Optimally Suppress Central Nervous System Autoimmunity

2020 ◽  
Vol 205 (2) ◽  
pp. 359-368
Author(s):  
Alexander W. Boyden ◽  
Ashley A. Brate ◽  
Laura M. Stephens ◽  
Nitin J. Karandikar
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
Ifn Γ

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

scholarly journals Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge

2004 ◽  
Vol 85 (8) ◽  
pp. 2379-2387 ◽  
Author(s):  
Ulrike Fassnacht ◽  
Andreas Ackermann ◽  
Peter Staeheli ◽  
Jürgen Hausmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Recombinant Vaccinia Virus ◽  
Immune Memory ◽  
Cervical Lymph Nodes ◽  
The Central Nervous System

Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2k mice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.

scholarly journals Critical Roles of NK and CD8+T Cells in Central Nervous System Listeriosis

2009 ◽  
Vol 182 (10) ◽  
pp. 6360-6368 ◽  
Author(s):  
Toshiyuki Hayashi ◽  
Shigenori Nagai ◽  
Hideki Fujii ◽  
Yukiko Baba ◽  
Eiji Ikeda ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells

scholarly journals Protective Immunosurveillance of the Central Nervous System by Listeria-Specific CD4 and CD8 T Cells in Systemic Listeriosis in the Absence of Intracerebral Listeria

2002 ◽  
Vol 169 (4) ◽  
pp. 2010-2019 ◽  
Author(s):  
Lai-Yu Kwok ◽  
Hrvoje Miletic ◽  
Sonja Lütjen ◽  
Sabine Soltek ◽  
Martina Deckert ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd8 T Cells ◽  
The Central Nervous System

Myeloid cells: The Trojan horse for T cell invasion into the brain

2019 ◽  
Vol 11 (520) ◽  
pp. eaaz9757
Author(s):  
Gilbert Gallardo
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cell Invasion ◽  
Myeloid Cells ◽  
Autoimmune Encephalomyelitis ◽  
Lectin Receptors ◽  
The Central Nervous System ◽  
The Brain ◽  
Experimental Autoimmune

C-type lectin receptors on myeloid cells regulate the activation and infiltration of T cells into the central nervous system in experimental autoimmune encephalomyelitis.

Sign in / Sign up

Export Citation Format

Share Document