title: The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages.
abstract: BACKGROUND
  Legionella pneumophila is an intracellular bacterial pathogen that invades and replicates within alveolar macrophages through injection of ∼ 300 effector proteins by its Dot/Icm type IV translocation apparatus. The bona fide F-box protein, AnkB, is a nutritional virulence effector that triggers macrophages to generate a surplus of amino acids, which is essential for intravacuolar proliferation. Therefore, the ankB mutant represents a novel genetic tool to determine the transcriptional response of human monocyte-derived macrophages (hMDMs) to actively replicating L. pneumophila.
  
  
  RESULTS
  Here, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila. The transcriptomes of hMDMs infected with either actively proliferating wild type or non-replicative ankB mutant bacteria were remarkably similar. The transcriptome of infected hMDMs was predominated by up-regulation of inflammatory pathways (IL-10 anti-inflammatory, interferon signaling and amphoterin signaling), anti-apoptosis, and down-regulation of protein synthesis pathways. In addition, L. pneumophila modulated diverse metabolic pathways, particularly those associated with bio-active lipid metabolism, and SLC amino acid transporters expression.
  
  
  CONCLUSIONS
  Taken together, the hMDM transcriptional response to L. pneumophila is independent of intra-vacuolar replication of the bacteria and primarily involves modulation of the immune response and metabolic as well as nutritional pathways.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, KY, 40202, United States of America.
authors.forename: Christopher T D
authors.initials: CT
authors.lastname: Price
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, KY, 40202, United States of America; Center for Predictive Medicine, University of Louisville, KY, 40202, United States of America.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Abu Kwaik
mesh_terms: D017487:Ankyrins / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics* / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000235:genetics* / Q000382:microbiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D009000:Monocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014617:Vacuoles / Q000235:genetics / Q000382:microbiology; D014774:Virulence / Q000235:genetics
chemical_list: D017487:Ankyrins; D015415:Biomarkers; D012333:RNA, Messenger