title: Impaired Toll-like receptor 2 signalling in monocytes from 5-year-old allergic children.
abstract: 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)-1 beta, 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.
authors.affiliation: Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. petra.amoudruz@imun.su.se
authors.forename: P
authors.initials: P
authors.lastname: Amoudruz
authors.forename: U
authors.initials: U
authors.lastname: Holmlund
authors.forename: S
authors.initials: S
authors.lastname: Saghafian-Hedengren
authors.forename: C
authors.initials: C
authors.lastname: Nilsson
authors.forename: E
authors.initials: E
authors.lastname: Sverremark-Ekström
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood; D015850:Interleukin-6 / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology; D017452:Receptors, IgG; D015398:Signal Transduction / Q000502:physiology*; D012882:Skin Tests; D051195:Toll-Like Receptor 2 / Q000032:analysis / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D017452:Receptors, IgG; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007073:Immunoglobulin E