title: Penicillin-binding protein of Ehrlichia chaffeensis: cytokine induction through MyD88-dependent pathway.
abstract: BACKGROUND
  Human monocytic ehrlichiosis is one of the most prevalent tick-borne zoonoses caused by infection with Ehrlichia chaffeensis. Although E. chaffeensis lacks entire lipopolysaccharide and most peptidoglycan biosynthesis genes, it induces inflammatory cytokines and chemokines. Ehrlichia chaffeensis components that induce inflammation and the responsive host cell pathway are not known.
  
  
  METHODS
  Expression of penicillin-binding protein (PBP) in E. chaffeensis was analyzed by reverse-transcription polymerase chain reaction and Bocillin FL binding assay. Next, recombinant PBP, which was high-pressure liquid chromatography purified, and native PBP of E. chaffeensis were investigated for their ability to induce proinflammatory cytokines in the human monocytic leukemia cell line THP-1 and bone marrow-derived macrophages (BMDMs) from wild-type and MyD88 knockout mice.
  
  
  RESULTS
  Expression of PBP by E. chaffeensis was upregulated during its intracellular life cycle. PBP induced interleukin 8 or CXCL2, tumor necrosis factor α, interleukin 1β, and interleukin 10 in THP-1 cells and BMDMs. Cytokine induction by PBP was MyD88-dependent. Removal of PBP from E. chaffeensis lysate using penicillin affinity column and a complementation assay confirmed cytokine-inducing activity of native PBP.
  
  
  CONCLUSIONS
  The cytokine-inducing activity by E. chaffeensis PBP provides novel insights into pathogen-associated molecular patterns and pathogenesis of E. chaffeensis infection.
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1093, USA.
authors.forename: Mohd Akhlakur
authors.initials: MA
authors.lastname: Rahman
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Cheng
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuo
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Rikihisa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018469:Ehrlichia chaffeensis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016873:Ehrlichiosis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D054426:Chemokine CXCL2; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D053594:Myeloid Differentiation Factor 88; D046915:Penicillin-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10