title: Differences in innate immune responses upon stimulation with gram-positive and gram-negative bacteria.
abstract: OBJECTIVE
  Host recognition pathways for gram-negative and gram-positive bacteria comprise pattern recognition receptors among which Toll-like receptors (TLRs) play a pivotal role. TLRs share common signaling pathways yet exhibit specificity as well. Periodontal disease is initiated and maintained in the first line by gram-negative but also gram-positive bacterial infection of the gingival sulcus. To date only limited information is available on whether gram-positive and gram-negative bacteria induce different host responses (strength or quality).
  
  
  METHODS
  To elucidate these differential effects we focused on proinflammatory cytokine releases by assessing ex vivo stimulation of whole blood with heat-killed gram-negative and gram-positive bacteria and thereof derived microbial products associated with distinct TLRs. Tumor necrosis factor-alpha and interleukin-8 release were measured in the supernatants by enzyme-linked immunosorbent assay. In addition, innate immune responses of peritoneal macrophages from mice lacking TLR2 and TLR4 were tested.
  
  
  RESULTS
  We observed that gram-negative and gram-positive species induced distinct patterns of cytokine production. Gram-negative species produced higher amounts of tumor necrosis factor-alpha while gram-positive species released higher amounts of the chemokine interleukin-8. Data from TLR knockout mice and TLR-transfected HEK cells revealed a somehow specific role of TLR4 and TLR2 for the recognition of gram-negative and gram-positive bacteria, respectively, an observation that goes along with the dominant recognition of the respective pathogen associated molecular patterns lipopolysaccharide and lipoteichoic acid.
  
  
  CONCLUSIONS
  The results show that gram-negative and gram-positive bacterial species induce different patterns of immunoregulatory activity, which might be the result of activation of different TLRs.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Philipps University, Marburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Tietze
authors.forename: Alexander
authors.initials: A
authors.lastname: Dalpke
authors.forename: Sigfried
authors.initials: S
authors.lastname: Morath
authors.forename: Reinier
authors.initials: R
authors.lastname: Mutters
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
authors.forename: Claudia
authors.initials: C
authors.lastname: Nonnenmacher
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood
chemical_list: D000942:Antigens, Bacterial; D016209:Interleukin-8; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha