title: Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study.
abstract: BACKGROUND
  Chlamydia pneumoniae causes respiratory infection in adults and children, and has been associated with asthma exacerbations and induction of Immunoglobulin (Ig) E responses. We previously reported that C. pneumoniae enhances T helper (Th) 2 responses of peripheral blood mononuclear cells (PBMC) from asthmatic patients. It is likely that toll like receptor (TLR)-2 and TLR-4 mediate cytokine responses and host defense against C. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model.
  
  
  METHODS
  PBMC (1.5 × 106) from asthmatic patients (N = 10) and non-asthmatic controls (N = 5) were infected or mock-infected for 1 h ± C. pneumoniae TW183 at a multiplicity of infection (MOI) = 1 and MOI = 0.1, and cultured for 48 h ± anti- TLR-2 and TLR-4 antibodies (Abs) (1 mg/mL). Interleukin (IL)-12 (48 h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA).
  
  
  RESULTS
  High IgE levels were detected in supernatants of C. pneumoniae- infected PBMC from asthmatics on day 10, compared with mock-infected PBMC (p < 0.03). In contrast, IgE was not detected (<0.3 ng/mL) in either C. pneumoniae infected or mock-infected PBMC from non-asthmatics. IL-12 production by C. pneumoniae-infected asthmatic and non-asthmatic PBMC were similar. When anti-TLR4, but not anti-TLR2, was included in culture, IL-12 production by C. pneumoniae- infected asthmatic PBMC decreased.
  
  
  CONCLUSIONS
  C. pneumoniae infection induces IgE production and modulates IL-12 responses in patients with asthma, which may be caused, in part, by differences in TLR-2 and TLR-4 stimulation.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA. tamar.smith-norowitz@downstate.edu.
authors.forename: T A
authors.initials: TA
authors.lastname: Smith-Norowitz
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA.
authors.forename: J
authors.initials: J
authors.lastname: Perlman
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Norowitz
authors.affiliation: Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, 11203, USA.
authors.forename: R
authors.initials: R
authors.lastname: Joks
authors.affiliation: Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, NY, 11203, USA.
authors.forename: H G
authors.initials: HG
authors.lastname: Durkin
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Hammerschlag
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kohlhoff
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D023521:Chlamydophila Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D007073:Immunoglobulin E
keywords: Asthma; C. pneumoniae; Interleukin-12; Toll like receptors