title: Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways.
abstract: Macrophages from the C57BL/6 (B6) mouse strain restrict intracellular growth of Legionella pneumophila, whereas A/J macrophages are highly permissive. The mechanism by which B6 macrophages restrict Legionella growth remains poorly understood, but is known to require the cytosolic microbe sensors Naip5 (Birc1e) and Ipaf. We hypothesized that Naip5 and Ipaf may act in partnership with other antimicrobial signalling pathways in macrophages. Indeed, we found that macrophages lacking either tumour necrosis factor (TNF)-alpha or type I interferon (IFN) signalling are permissive for growth of L. pneumophila, even in the presence of functional Naip5 and Ipaf alleles. Similarly, macrophages lacking Naip5 and/or Ipaf signalling were permissive even though we found that Naip5 or Ipaf were not required for induction of TNF-alpha and type I IFN. Therefore, our data suggest that the mechanism by which B6 macrophages restrict intracellular replication of L. pneumophila is more complex than previously appreciated, and involves the concerted action of cytokine and intracellular microbe sensor signalling pathways.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. jcoers@genetics.med.harvard.edu
authors.forename: Jörn
authors.initials: J
authors.lastname: Coers
authors.forename: Russell E
authors.initials: RE
authors.lastname: Vance
authors.forename: Mary F
authors.initials: MF
authors.lastname: Fontana
authors.forename: William F
authors.initials: WF
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D016952:Legionella pneumophila / Q000502:physiology*; D008163:Luminescent Measurements; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D007370:Interferon Type I; C512299:Ipaf protein, mouse; C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D014409:Tumor Necrosis Factor-alpha