title: Legionella longbeachae Is Immunologically Silent and Highly Virulent In Vivo.
abstract: BACKGROUND
  Legionella longbeachae (Llo) and Legionella pneumophila (Lpn) are the most common pneumonia-causing agents of the genus. Although both species can be lethal to humans and are highly prevalent, little is known about the molecular pathogenesis of Llo infections. In murine models of infection, Lpn infection is self-limited, whereas Llo infection is lethal.
  
  
  METHODS
  We used mouse macrophages, human macrophages, human epithelial cells, and mouse infections in vivo to evaluate multiple parameters of the infection.
  
  
  RESULTS
  We determined that the Llo Dot/Icm secretion system is critical for virulence. Different than Lpn, Llo disseminates and the animals develop a severe pulmonary failure, as demonstrated by lung mechanics and blood oxygenation assays. As compared to Lpn, Llo is immunologically silent and fails to trigger the production of cytokines in human pulmonary epithelial cells and in mouse and human macrophages. Infections in Tnfr1-/-, Ifng-/-, and Il12p40-/- mice supported the participation of cytokines for the resistance phenotype.
  
  
  CONCLUSIONS
  Both Lpn and Llo require the Dot/Icm system for pathogenesis, but the infection outcome is strikingly different. Llo is immunologically silent, highly virulent, and lethal. The differences reported herein may reflect unappreciated clinical differences in patients infected with Lpn or Llo.
authors.affiliation: Department of Cell Biology.
authors.forename: Liliana M
authors.initials: LM
authors.lastname: Massis
authors.affiliation: Department of Cell Biology.
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Assis-Marques
authors.affiliation: Department of Pharmacology, and.
authors.forename: Fernanda V S
authors.initials: FV
authors.lastname: Castanheira
authors.affiliation: Department of Cell Biology.
authors.forename: Yasmin J
authors.initials: YJ
authors.lastname: Capobianco
authors.affiliation: Department of Medical Clinic, School of Medicine of Ribeirão Preto, University of São Paulo, FMRP/USP, Ribeirão Preto,Brazil.
authors.forename: Andiamira C
authors.initials: AC
authors.lastname: Balestra
authors.affiliation: Biology of Intracellular Bacteria, Institut Pasteur, and.|CNRS UMR 3525, Paris, France ; and.
authors.forename: Pedro
authors.initials: P
authors.lastname: Escoll
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victoria, Australia.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Wood
authors.affiliation: Department of Cell Biology.
authors.forename: Graziele Z
authors.initials: GZ
authors.lastname: Manin
authors.affiliation: Department of Cell Biology.
authors.forename: Vani M A
authors.initials: VM
authors.lastname: Correa
authors.affiliation: Department of Pharmacology, and.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Department of Pharmacology, and.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Biology of Intracellular Bacteria, Institut Pasteur, and.|CNRS UMR 3525, Paris, France; and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
authors.affiliation: Department of Medical Clinic, School of Medicine of Ribeirão Preto, University of São Paulo, FMRP/USP, Ribeirão Preto,Brazil.
authors.forename: Marcos C
authors.initials: MC
authors.lastname: Borges
authors.affiliation: The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victoria, Australia.
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: Newton
authors.affiliation: Department of Cell Biology.
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D060467:Disease Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D044128:Legionella longbeachae / Q000276:immunology* / Q000472:pathogenicity*; D016952:Legionella pneumophila / Q000276:immunology; D007876:Legionellosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D007963:Leukocytes, Mononuclear; D008168:Lung / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D014774:Virulence
chemical_list: D016207:Cytokines
keywords: Legionella longbeachae; Type IV secretion system; macrophages.; pulmonary infection