Dataset Information

Exoenzyme T Plays a Pivotal Role in the IFN-? Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells.

ABSTRACT: Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia mouse model. Human NK cells or NK92 cell line produced low levels of IFN-? in response to PA without IL-12 stimulation, whereas PA significantly increased IFN-? after IL-12 priming. The modulation of IFN-? production by PA required bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates IFN-? production and control ERK activation. In vivo, ExoT also increases IFN-? levels and the percentage of IFN-?+ NK cells in lungs during PA pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS could modulate the production of IFN-? by NK cells after PA infection through ERK activation.

SUBMITTER: Vourc'h M

PROVIDER: S-EPMC5641345 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after <i>Pseudomonas</i> Challenge in IL-12 Primed Natural Killer Cells.

Vourc'h Mickael M Roquilly Antoine A Broquet Alexis A David Gaelle G Hulin Philippe P Jacqueline Cedric C Caillon Jocelyne J Retiere Christelle C Asehnoune Karim K

Frontiers in immunology 20171010

<i>Pseudomonas aeruginosa</i> (PA) expresses the type III secretion system (T3SS) and effector exoenzymes that interfere with intracellular pathways. Natural killer (NK) cells play a key role in antibacterial immunity and their activation is highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell interactions and the role of IL-12 using human peripheral blood mononuclear cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild-type (WT) strain of PA (P ...[more]

PMID: 29067027

Similar Datasets

Project description:RationaleComplement activation contributes to multiple immune-mediated pathologies. In late allograft failure, donor-specific antibody deposits complement membrane attack complexes (MAC) on graft endothelial cells (ECs), substantially increasing their immunogenicity without causing lysis. Internalized MAC stabilize NIK (NF-κB [nuclear factor kappa-light-chain-enhancer of activated B cells]-inducing kinase) protein on Rab5+MAC+ endosomes, activating noncanonical NF-κB signaling. However, the link to increased immunogenicity is unclear.ObjectiveTo identify mechanisms by which alloantibody and internalized MAC activate ECs to enhance their ability to increase T-cell responses.Methods and resultsIn human EC cultures, internalized MAC also causes NLRP3 (NOD-like receptor family pyrin domain containing 3) translocation from endoplasmic reticulum to Rab5+MAC+NIK+ endosomes followed by endosomal NIK-dependent inflammasome assembly. Cytosolic NIK, stabilized by LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells), does not trigger inflammasome assembly, and ATP-triggered inflammasome assembly does not require NIK. IFN-γ (interferon-γ) primes EC responsiveness to MAC by increasing NLRP3, pro-caspase 1, and gasdermin D expression. NIK-activated noncanonical NF-κB signaling induces pro-IL (interleukin)-1β expression. Inflammasome processed pro-IL-1β, and gasdermin D results in IL-1β secretion that increases EC immunogenicity through IL-1 receptor signaling. Activation of human ECs lining human coronary artery grafts in immunodeficient mouse hosts by alloantibody and complement similarly depends on assembly of an NLRP3 inflammasome. Finally, in renal allograft biopsies showing chronic rejection, caspase-1 is activated in C4d+ ECs of interstitial microvessels, supporting the relevance of the cell culture findings.ConclusionsIn response to antibody-mediated complement activation, IFN-γ-primed human ECs internalize MAC, triggering both endosomal-associated NIK-dependent NLRP3 inflammasome assembly and IL-1 synthesis, resulting in autocrine/paracrine IL-1β-mediated increases in EC immunogenicity. Similar responses may underlie other complement-mediated pathologies.

Dataset Information

Exoenzyme T Plays a Pivotal Role in the IFN-? Production after Pseudomonas Challenge in IL-12 Primed Natural Killer Cells.

Publications

Exoenzyme T Plays a Pivotal Role in the IFN-γ Production after <i>Pseudomonas</i> Challenge in IL-12 Primed Natural Killer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets