Toll-like receptors pathway in common variable immune deficiency (CVID) and X-linked agammaglobulinemia (XLA).

Abstract

Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two major humoral immunodeficiencies, causing a high rate of early age mortality in children. In order to identifiy the possible factors involved in the pathogenesis of CVID and XLA, recent studies have focused on Toll-like receptors (TLRs) and demonstrate the defects in different TLR pathways in immune cells of CVID and XLA patients. Herein, we measured TLR-4 and TLR-9 RNA levels and consequently TNF-α and IFN-α production in peripheral blood mononuclear cells (PBMCs) of patients with CVID and XLA. Contrary to healthy individuals, TLR-9 expression was not significantly increased after ligand stimulation, whereas ligand-induced TLR-4 expression was not significantly different from that in healthy control PBMCs. Lipopolysaccharide (LPS)-stimulated TNF-α production was significantly reduced in patients compared to controls, whereas IFN-α production was increased in all groups after CpG stimulation without any significant inter-group difference. Our data suggest that defects in TLR-9 activated pathways may be a result of the decreased TLR-9 expression, although TLR-9 is not the only modulator of IFN-α production in these patients. On the other hand, impaired signaling in TLR-4 activated pathways which results in significant reduction in TNF-α production are not related to a defect in TLR-4 expression.

• Authors: Parsova Tavasolian, Laleh Sharifi, Asghar Aghamohammadi, Farshid Noorbakhsh, Rouzbeh Sanaei, Mahsima Shabani, Nima Rezaei
• Journal: European cytokine network (Eur Cytokine Netw) Vol. 29 Issue 4 Pg. 153-158 (Nov 01 2018) ISSN: 1952-4005 [Electronic] France
• PMID: 30698158 (Publication Type: Journal Article)

Chemical References

• Ligands
• Lipopolysaccharides
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha

Topics

• Adolescent
• Adult
• Agammaglobulinemia (metabolism)
• Child
• Common Variable Immunodeficiency (metabolism)
• Genetic Diseases, X-Linked (metabolism)
• Humans
• Leukocytes, Mononuclear (drug effects, metabolism)
• Ligands
• Lipopolysaccharides (pharmacology)
• Male
• Signal Transduction (drug effects, physiology)
• Toll-Like Receptors (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Young Adult