title: Staphylococcus aureus Adenosine Inhibits sPLA2-IIA-Mediated Host Killing in the Airways.
abstract: Staphylococcus aureus is a common cause of bacterial infections in respiratory diseases. It secretes molecules to dampen host immunity, and the recently identified adenosine is one of these molecules. The type IIA secretory phospholipase A2 (sPLA2-IIA) is a host protein endowed with antibacterial properties, especially against Gram-positive bacteria such as S. aureus. However, the role of adenosine in sPLA2-IIA-mediated S. aureus killing by host is still unknown. The present studies showed that the S. aureus mutant lacking adenosine production (∆adsA strain) increased sPLA2-IIA expression in guinea pig airways and was cleared more efficiently, compared with the wild-type strain. S. aureus ∆adsA strain induced sPLA2-IIA expression by alveolar macrophages after phagocytic process via NOD2-NF-κB-dependent mechanism. However, S. aureus adenosine (wild-type and adsA-complemented strains) and exogenous adenosine downregulated S. aureus phagocytosis by alveolar macrophages, leading to inhibition of sPLA2-IIA expression. This occurred through inhibition of p38 phosphorylation via adenosine receptors A2a-, A2b-, and protein kinase A-dependent pathways. Taken together, our studies suggest that, in the airway, S. aureus escapes sPLA2-IIA-mediated killing through adenosine-mediated inhibition of phagocytosis and sPLA2-IIA expression.
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France; Cellule Pasteur-Université Pierre et Marie Curie, 75015 Paris, France;
authors.forename: Erwan
authors.initials: E
authors.lastname: Pernet
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France; Faculté des Sciences, Campus Universitaire d'Orsay, Université Paris-Sud, 91405 Orsay, France; and.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Brunet
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Guillemot
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France; yongzheng.wu@pasteur.fr touqui@pasteur.fr.
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.affiliation: Unité de Défense Innée et Inflammation/INSERM U874, Institut Pasteur, 75015 Paris, France; Unité de Biologie Cellulaire de l'Infection Microbienne, Institut Pasteur, 75015 Paris, France yongzheng.wu@pasteur.fr touqui@pasteur.fr.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000241:Adenosine / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006168:Guinea Pigs; D054884:Host-Pathogen Interactions; D007093:Imidazoles / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007093:Imidazoles; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; D011725:Pyridines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054501:Group II Phospholipases A2; D000241:Adenosine; C093642:SB 203580