title: Cyclic dinucleotides modulate human T-cell response through monocyte cell death.
abstract: Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c-di-AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T-cell response comprised cell-cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c-di-AMP- or cGAMP-primed apoptotic monocytes.
authors.affiliation: INSERM UMR1037-Centre de Recherches en Cancerologie de Toulouse, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.|ERL 5294 CNRS, Toulouse, France.|Laboratoire d'Excellence 'TOUCAN', Toulouse, France.|Institut Carnot 'CALYM', Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tosolini
authors.affiliation: INSERM UMR1037-Centre de Recherches en Cancerologie de Toulouse, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pont
authors.affiliation: CIRI, EVIR team, Inserm U1111, CNRS UMR5308, Université de Lyon-1, ENS de Lyon, Lyon, France.|Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire, Nice, France.
authors.forename: Els
authors.initials: E
authors.lastname: Verhoeyen
authors.affiliation: INSERM UMR1037-Centre de Recherches en Cancerologie de Toulouse, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.|ERL 5294 CNRS, Toulouse, France.|Laboratoire d'Excellence 'TOUCAN', Toulouse, France.|Institut Carnot 'CALYM', Toulouse, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1 / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D015226:Dinucleoside Phosphates; D009712:Nucleotides, Cyclic; C528998:cyclic diadenosine phosphate; C584311:cyclic guanosine monophosphate-adenosine monophosphate; D020170:Caspase 1
keywords: A2a adenosine receptor; Activation; Cyclic dinucleotides; Quiescence; T lymphocytes