title: Chemokine, cytokine and type I interferon production induced by Toll-like receptor activation in common variable immune deficiency.
abstract: Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency and is associated with recurrent infections and chronic inflammatory diseases. We evaluated the ability of Toll-like receptor (TLR) ligands to induce secretion of chemokines, cytokines and type I interferons by peripheral blood mononuclear cells (PBMCs) from CVID patients. High levels of CXCL10, CCL2, CXCL9, CCL5, CXCL8, and IL-6 were detected in sera of CVID patients compared with healthy controls. Increased chemokine levels were observed in unstimulated PBMCs, but after stimulation with TLR2 and TLR4 agonists, equivalent chemokine and pro-inflammatory cytokine secretion, as in healthy controls, was observed, whereas TLR4 agonist induced a decreased secretion of CCL2 and CXCL8 and increased secretion of TNF. Decreased IFN-α secretion induced by TLR7/TLR8 activation was observed in CVID, which was recovered with TLR9 signaling. Our findings revealed that TLR9 activation has an adjuvant effect on the altered type I response in CVID.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Camila de
authors.initials: C
authors.lastname: Lollo
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Dewton
authors.initials: D
authors.lastname: de Moraes Vasconcelos
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Luanda Mara da Silva
authors.initials: LMDS
authors.lastname: Oliveira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Domingues
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Gabriel Costa de
authors.initials: GC
authors.lastname: Carvalho
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Alberto José da Silva
authors.initials: AJDS
authors.lastname: Duarte
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil. Electronic address: marisato@usp.br.
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C547051:CL097 compound; D018925:Chemokines; D016207:Cytokines; D007093:Imidazoles; D007370:Interferon Type I; D008024:Ligands; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D011804:Quinolines; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D011070:Poly I-C
keywords: Chemokines; Common variable immunodeficiency; Cytokines; Toll-like receptor agonists