Impact of asthma, environmental exposures and ethnicity on functional responsiveness to Toll-like receptor (TLR) stimulation in children
|Lissitsyn, Yuriy V
|Becker, Allan (Pediatrics and Child Health) Marshall, Aaron (Immunology)Yang, Xi (Medical Microbiology)
|HayGlass, Kent (Immunology)
|Master of Science (M.Sc.)
|TLRs play a key role in initiating innate immunity and in regulating the nature of the adaptive immune response. We hypothesized that functional responsiveness to TLR stimulation differs in clinically; environmentally; ethnically distinct pediatric populations. PBMC obtained from 272 children were stimulated with a panel of TLR ligands. Levels of pro- and anti-inflammatory, Th1-, Th2-associated cytokines were quantified by ELISA. We demonstrate that use of threshold concentrations of TLR4 and TLR2 ligands reveal striking differences in cytokine responses between asthmatic and non-atopic children. Specifically, non-atopic controls produce higher levels of pro-inflammatory cytokines, whereas asthmatics exhibit increased anti-inflammatory IL-10 responses. Asthmatic children exposed to environmental tobacco smoke (ETS) demonstrated elevated levels of chemokines relative to non-ETS exposed asthmatics and controls. First Nation children favor anti-inflammatory IL-10 responses, whereas Caucasian population respond to TLR activation by production of more robust pro-inflammatory and Th1 biased cytokine and chemokine responses.
|Impact of asthma, environmental exposures and ethnicity on functional responsiveness to Toll-like receptor (TLR) stimulation in children