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

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 againstC. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model. PBMC (1.5×106) from asthmatic patients (N=10) and non-asthmatic controls (N=5) were infected or mock-infected for 1h±C. pneumoniae TW183 at a multiplicity of infection (MOI)=1 and MOI=0.1, and cultured for 48h±anti- TLR-2 and TLR-4 antibodies (Abs) (1mg/mL). Interleukin (IL)-12 (48h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA). 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 (<0.3ng/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. 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.