Intravenous Immunoglobulin (IVIg) is mainly composed of IgG derived from pooled plasma of healthy individuals and used to treat a variety of immune diseases. Low dose administration can activate the immune system in cases of immunodeficiencies, while high doses suppress immune responses in autoimmune/autoinflammatory conditions. The mechanisms underlying the effects of this therapeutic, especially in the cases of immunodeficiencies, are poorly understood. Most immunodeficient patients suffer from persistent fungal, bacterial and viral infections which sign major defects in innate immune cells such as monocytes.
Lasting (weeks to months) immunomodulation in innate immune cells can reflect a type of immune memory, which is known as "trained immunity". There are several pattern recognition receptor ligands, such as β-glucan, known to induce trained immunity which leads to greater responses to re-infections. Herein, we investigated whether IVIg can induce trained immunity or not upon the knowledge of activating effects of IVIg on innate immune cells.
Therefore, we explored the possible role of IVIg in inducing trained immunity in monocytes. For this purpose, we trained THP1-Dual cells with IVIg parallel to other reprogramming controls (LPS and PGN). Functional assays based on ROS-production, secondary pro-inflammatory cytokine secretion and NF-κB activation showed that IVIg is a potent inducer of trained immunity, capable of increasing recall responses to bacterial, fungal and/or viral ligands.