Chemokine, cytokine and type I interferon production induced by Toll-like receptor activation in common variable immune deficiency

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2016-08, Vol.169, p.121-127
• Main Authors: de Lollo, Camila, de Moraes Vasconcelos, Dewton, da Silva Oliveira, Luanda Mara, Domingues, Rosana, de Carvalho, Gabriel Costa, da Silva Duarte, Alberto José, Sato, Maria Notomi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allergy and Immunology; Cells, Cultured; Chemokines; Chemokines - blood; Chemokines - immunology; Chemokines - secretion; Common variable immunodeficiency; Common Variable Immunodeficiency - blood; Common Variable Immunodeficiency - immunology; Common Variable Immunodeficiency - metabolism; Cytokines; Cytokines - blood; Cytokines - immunology; Cytokines - secretion; Female; Humans; Imidazoles - pharmacology; Interferon Type I - biosynthesis; Interferon Type I - blood; Interferon Type I - immunology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Ligands; Lipopolysaccharides - pharmacology; Male; Middle Aged; Oligodeoxyribonucleotides - pharmacology; Poly I-C - pharmacology; Quinolines - pharmacology; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 7 - immunology; Toll-Like Receptor 7 - metabolism; Toll-Like Receptor 8 - agonists; Toll-Like Receptor 8 - immunology; Toll-Like Receptor 8 - metabolism; Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism; Toll-like receptor agonists; Toll-Like Receptors - agonists; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; Young Adult
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2016.07.001

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.