Impaired Toll‐like receptor 2 signalling in monocytes from 5‐year‐old allergic children
The relative composition of the two major monocytic subsets CD14+CD16− and CD14+CD16+ is altered in some allergic diseases. These two subsets display different patterns of Toll‐like receptor levels, which could have implications for activation of innate immunity leading to reduced immunoglobulin E‐specific adaptive immune responses. This study aimed to investigate if allergic status at the age of 5 years is linked to differences in monocytic subset composition and their Toll‐like receptor levels, and further, to determine if Toll‐like receptor regulation and cytokine production upon microbial stimuli is influenced by the allergic phenotype. Peripheral blood mononuclear cells from 5‐year‐old allergic and non‐allergic children were stimulated in vitro with lipopolysaccharide and peptidoglycan. Cells were analysed with flow cytometry for expression of CD14, Toll‐like receptors 2 and 4 and p38‐mitogen‐activated protein kinase (MAPK). The release of cytokines and chemokines [tumour necrosis factor, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐12p70] into culture supernatants was measured with cytometric bead array. For unstimulated cells there were no differences in frequency of the monocytic subsets or their Toll‐like receptor levels between allergic and non‐allergic children. However, monocytes from allergic children had a significantly lower up‐regulation of Toll‐like receptor 2 upon peptidoglycan stimulation. Further, monocytes from allergic children had a higher spontaneous production of IL‐6, but there were no differences between the two groups regarding p38‐MAPK activity or cytokine and chemokine production upon stimulation. The allergic subjects in this study have a monocytic population that seems to display a hyporesponsive state as implicated by impaired regulation of Toll‐like receptor 2 upon peptidoglycan stimulation.