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

- CVID patients present recurrent or chronic infections, which may disturb innate immunity reflecting in the chemokines serum levels.
- Activation of Toll-like receptor 4 (TLR4) induces impaired CCL2 and CXCL8 secretion while enhancing TNF secretion in CVID.
- The TLR7/TLR8 agonist acts as an adjuvant of innate immune responses and induces chemokine and cytokine production.
- CVID patients showed impaired type I interferon production by peripheral blood mononuclear cells that was induced by TLR7 agonist.
- Type I interferon was restored with TLR7/TLR8 agonist and up-regulated with TLR9 agonist in some CVID patients.

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.