title: Extracellular adenosine triphosphate affects the response of human macrophages infected with Mycobacterium tuberculosis.
abstract: Granulomas are the hallmark of Mycobacterium tuberculosis infection. As the host fails to control the bacteria, the center of the granuloma exhibits necrosis resulting from the dying of infected macrophages. The release of the intracellular pool of nucleotides into the surrounding medium may modulate the response of newly infected macrophages, although this has never been investigated. Here, we show that extracellular adenosine triphosphate (ATP) indirectly modulates the expression of 272 genes in human macrophages infected with M. tuberculosis and that it induces their alternative activation. ATP is rapidly hydrolyzed by the ecto-ATPase CD39 into adenosine monophosphate (AMP), and it is AMP that regulates the macrophage response through the adenosine A2A receptor. Our findings reveal a previously unrecognized role for the purinergic pathway in the host response to M. tuberculosis. Dampening inflammation through signaling via the adenosine A2A receptor may limit tissue damage but may also favor bacterial immune escape.
authors.affiliation: Unité de Génétique Mycobactérienne Cellule Pasteur, Université Paris Diderot, Sorbonne Paris Cité, Paris.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dubois-Colas
authors.affiliation: Unité de Génétique Mycobactérienne Cellule Pasteur, Université Paris Diderot, Sorbonne Paris Cité, Paris.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Petit-Jentreau
authors.affiliation: Sainte-Justine Hospital Research Centre, Department of Pediatrics, Faculty of Medicine, University of Montreal, Canada.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.affiliation: Département de Radio-Pharmacologie, Institut Curie-Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Sylvère
authors.initials: S
authors.lastname: Durand
authors.affiliation: Plate-forme Transcriptome et Epigénome, Département Génomes et Génétique, Institut Pasteur.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Soubigou
authors.affiliation: Unité de Génétique Mycobactérienne.
authors.forename: Cécile
authors.initials: C
authors.lastname: Lecointe
authors.affiliation: Unité de Génétique Mycobactérienne.
authors.forename: Jihène
authors.initials: J
authors.lastname: Klibi
authors.affiliation: Département de Radio-Pharmacologie, Institut Curie-Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Rezaï
authors.affiliation: Département de Radio-Pharmacologie, Institut Curie-Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: François
authors.initials: F
authors.lastname: Lokiec
authors.affiliation: Plate-forme Transcriptome et Epigénome, Département Génomes et Génétique, Institut Pasteur.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.affiliation: Unité de Génétique Mycobactérienne.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.affiliation: Unité de Génétique Mycobactérienne.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tailleux
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate
keywords: A2A receptor; AMP; ATP; Mycobacterium tuberculosis; alternative polarization; macrophages