title: Characterization of the murine macrophage response to infection with virulent and avirulent Burkholderia species.
abstract: BACKGROUND
  Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered.
  
  
  RESULTS
  The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt.
  
  
  CONCLUSIONS
  These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. chih-yuan.chiang.ctr@mail.mil.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: Institute for Therapeutic Innovation, Department of Medicine, University of Florida, Orlando, FL, USA. labrat29@yahoo.com.
authors.forename: Ricky L
authors.initials: RL
authors.lastname: Ulrich
authors.affiliation: Florida SouthWestern State College, Fort Myers, FL, USA. Melanie.Ulrich@fsw.edu.
authors.forename: Melanie P
authors.initials: MP
authors.lastname: Ulrich
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. brett.p.eaton.ctr@mail.mil.
authors.forename: Brett
authors.initials: B
authors.lastname: Eaton
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. ojedaj2011@gmail.com.
authors.forename: Jenifer F
authors.initials: JF
authors.lastname: Ojeda
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. douglas.j.lane.ctr@mail.mil.
authors.forename: Douglas J
authors.initials: DJ
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authors.affiliation: Perkin Elmer, Waltham, MA, USA. krishna.p.kota.ctr@mail.mil.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Kota
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. tara.a.kenny.ctr@mail.mil.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Kenny
authors.affiliation: Center for Genome Sciences, USAMRIID, Fort Detrick, MD, USA. jason.t.ladner.ctr@mail.mil.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Ladner
authors.affiliation: Office of Regulated Studies, USAMRIID, Fort Detrick, MD, USA. spdickson@gmail.com.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Dickson
authors.affiliation: Pathology Division, USAMRIID, Fort Detrick, MD, USA. kathleen.a.kuehl.civ@mail.mil.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kuehl
authors.affiliation: Pathology Division, USAMRIID, Fort Detrick, MD, USA. rahul.raychaudhuri.mil@mail.mil.
authors.forename: Rahul
authors.initials: R
authors.lastname: Raychaudhuri
authors.affiliation: Pathology Division, USAMRIID, Fort Detrick, MD, USA. mei.g.sun.ctr@mail.mil.
authors.forename: Mei
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authors.lastname: Sun
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. sina.bavari.civ@mail.mil.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.affiliation: Diagnostic Systems Division, USAMRIID, Fort Detrick, MD, USA. mark.j.wolcott.civ@mail.mil.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Wolcott
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD, USA. CovellD@mail.nih.gov.
authors.forename: David
authors.initials: D
authors.lastname: Covell
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA. rekha.g.panchal.civ@mail.mil.
authors.forename: Rekha G
authors.initials: RG
authors.lastname: Panchal
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D042726:Burkholderia mallei / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D018925:Chemokines / Q000235:genetics*; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000378:metabolism; D007113:Immunity, Innate; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D000067996:RAW 264.7 Cells
chemical_list: D000199:Actins; D018925:Chemokines