title: Impaired toll like receptor 9 response in pulmonary tuberculosis.
abstract: Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll-like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case-control study.
  
  
  
  PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24h with TLR 2 ligand (PAM-CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG-ODN)). Interleukin-8 (IL-8) was estimated in the supernatant by ELISA. Messenger RNA expression for inflammatory cytokines was quantitated using real time PCR.
  
  
  
  The important findings were (1) reduced PBMC secretion of IL-8 in response to all ligands in active TB; (2) normal to increased PBMC secretion of IL-8 in response to all ligands except CpG ODN (TLR 9 ligand) in TB patients who had recovered; (3) absence of difference in mRNA expression for a consortium of inflammatory pathway genes between healthy controls, active pulmonary tuberculosis and treated pulmonary tuberculosis patients.
  
  
  
  There was a generalized post-translational suppression of the IL-8 response to innate immune ligands in active TB. There appears to be a defect of TLR 9 signaling in patients with tuberculosis, the nature of which needs to be further explored.
authors: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632004, India. Electronic address: kartik_ramakrishna@hotmail.com.
authors: Kartik
authors: K
authors: Ramakrishna
authors: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632004, India.
authors: Kalpana
authors: K
authors: Premkumar
authors: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632004, India.
authors: Jayakanthan
authors: J
authors: Kabeerdoss
authors: Department of Community Health, Christian Medical College, Vellore 632004, India.
authors: K R
authors: KR
authors: John
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
chemical_list: C408982:CPG-oligonucleotide; C508606:CXCL8 protein, human; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D005408:Flagellin; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: CpG ODN; Lipopolysaccharide; NOD like receptors; Toll like receptors; Unmethylated DNA