title: Acute exposure to silica nanoparticles enhances mortality and increases lung permeability in a mouse model of Pseudomonas aeruginosa pneumonia.
abstract: BACKGROUND
  The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants. The consequences of nanoparticle exposure in the context of lung infection have not been studied in detail. Previous reports have shown that sequential lung exposure to nanoparticles and bacteria may impair bacterial clearance resulting in increased lung bacterial loads, associated with a reduction in the phagocytic capacity of alveolar macrophages.
  
  
  RESULTS
  Here we have studied the consequences of SiO2 nanoparticle exposure on Pseudomonas aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury in a mouse model of acute pneumonia. We observed that pre-exposure to SiO2 nanoparticles increased mice susceptibility to lethal pneumonia but did not modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain. Furthermore, internalisation of SiO2 nanoparticles by primary alveolar macrophages did not reduce the capacity of the cells to clear Pseudomonas aeruginosa. In our murine model, SiO2 nanoparticle pre-exposure preferentially enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by the measurement of alveolar albumin and IgM concentrations) rather than contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by leukocyte recruitment and cytokine concentration in the alveolar compartment).
  
  
  CONCLUSIONS
  We show that pre-exposure to SiO2 nanoparticles increases mice susceptibility to lethal pneumonia but independently of macrophage phagocytic function. The deleterious effects of SiO2 nanoparticle exposure during Pseudomonas aeruginosa-induced pneumonia are related to alterations of the alveolar-capillary barrier rather than to modulation of the inflammatory responses.
authors.affiliation: Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. mathilde.delaval@gmail.com.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Delaval
authors.affiliation: Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. boland@univ-paris-diderot.fr.
authors.forename: Sonja
authors.initials: S
authors.lastname: Boland
authors.affiliation: Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. brigitte.solhonne@inserm.fr.|INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. brigitte.solhonne@inserm.fr.|INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. brigitte.solhonne@inserm.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Solhonne
authors.affiliation: Plateforme d'imagerie dynamique, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. manicola@pasteur.fr.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nicola
authors.affiliation: CNRS, Univ. Bordeaux, ICMCB, UPR 9048, 87 Avenue du Docteur A. Schweitzer, Pessac cedex, F-33600, France. mornet@icmcb-bordeaux.cnrs.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mornet
authors.affiliation: Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. baeza@univ-paris-diderot.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Baeza-Squiban
authors.affiliation: Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.|INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.|INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. jean-michel.sallenave@inserm.fr.|Université Sorbonne Paris Cité, Cellule Pasteur, Université Paris Diderot, rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
authors.affiliation: Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.|INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.|INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. ignacio.garcia-verdugo@inserm.fr.|Université Sorbonne Paris Cité, Cellule Pasteur, Université Paris Diderot, rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garcia-Verdugo
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D002199:Capillary Permeability / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D019570:Inhalation Exposure; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000139:chemically induced* / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000139:chemically induced* / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects*; D064588:Selenium Oxides / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D064588:Selenium Oxides