title: Pathogenic bacterial species associated with endodontic infection evade innate immune control by disabling neutrophils.
abstract: Endodontic infections, in which oral bacteria access the tooth pulp chamber, are common and do not resolve once established. To investigate the effects of these infections on the innate immune response, we established a mouse subcutaneous chamber model, where a mixture of four oral pathogens commonly associated with these infections (endodontic pathogens [EP]), i.e., Fusobacterium nucleatum, Streptococcus intermedius, Parvimonas micra, and Prevotella intermedia, was inoculated into subcutaneously implanted titanium chambers. Cells that infiltrated the chamber after these infections were primarily neutrophils; however, these neutrophils were unable to control the infection. Infection with a nonpathogenic oral bacterial species, Streptococcus mitis, resulted in well-controlled infection, with bacterial numbers reduced by 4 to 5 log units after 7 days. Propidium iodide (PI) staining of the chamber neutrophils identified three distinct populations: neutrophils from EP-infected chambers were intermediate in PI staining, while cells in chambers from mice infected with S. mitis were PI positive (apoptotic) or negative (live). Strikingly, neutrophils from EP-infected chambers were severely impaired in their ability to phagocytose and to generate reactive oxygen species in vitro after removal from the chamber compared to cells from S. mitis-infected chambers. The mechanism of neutrophil impairment was necrotic cell death as determined by morphological analyses. P. intermedia alone could induce a similar neutrophil phenotype. We conclude that the endodontic pathogens, particularly P. intermedia, can efficiently disable and kill infiltrating neutrophils, allowing these infections to become established. These results can help explain the persistence of endodontic infections and demonstrate a new virulence mechanism associated with P. intermedia.
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA Harvard School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Aritsune
authors.initials: A
authors.lastname: Matsui
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Jun-O
authors.initials: JO
authors.lastname: Jin
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA Harvard School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Johnston
authors.affiliation: Harvard School of Dental Medicine, Boston, Massachusetts, USA Center for Biomineralization, Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Department of Prosthodontics, Faculty of Dental Medicine, The Hebrew University-Hadassah, Jerusalem, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Houri-Haddad
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA Harvard School of Dental Medicine, Boston, Massachusetts, USA srittling@forsyth.org.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rittling
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology*; D004195:Disease Models, Animal; D057131:Immune Evasion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011671:Pulpitis / Q000276:immunology* / Q000382:microbiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species