THP-1 cells increase TNF-α production upon LPS + soluble human IgG co-stimulation supporting evidence for TLR4 and Fcγ receptors crosstalk

• Published in: Cellular immunology 2020-09, Vol.355, p.104146-104146, Article 104146
• Main Authors: Vargas-Hernández, Omar, Ventura-Gallegos, José Luis, Ventura-Ayala, María Laura, Torres, Martha, Zentella, Alejandro, Pedraza-Sánchez, Sigifredo
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Crosstalk; Cytokines - metabolism; Fc gamma receptors; Human; Humans; Immunoglobulin G - pharmacology; Interleukin-1 Receptor-Associated Kinases - metabolism; Interleukin-2 - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Lymphocyte Antigen 96 - immunology; Lymphocyte Antigen 96 - metabolism; Macrophages - metabolism; Monocyte - macrophage; Monocytes - metabolism; NF-kappa B - metabolism; Receptor Cross-Talk - physiology; Receptors, IgG - immunology; Receptors, IgG - metabolism; Signal Transduction - drug effects; THP-1 Cells; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2020.104146

•TLR4, MD2 and Fc-γRs form part of the multimolecular receptor for LPS.•Aggregated IgG crosstalk with LPS and other TLR ligands to change cytokine production.•Soluble IgG (sIgG) + LPS increase TNF-α production in monocytes and THP-1 cells altering NF-κB pathway.•In vivo circulating sIgG may increase cytokine production during infection by a TLR4-Fc-γR crosstalk. The lipopolysaccharide (LPS) of Gram-negative bacteria is recognized on human monocytes and macrophages by TLR4 and MD2 and induces the production of inflammatory cytokines; the LPS + IgG complexes co-stimulation increases the cytokine production, mediated by the Fc-γRIIa (CD32a). We stimulated human CD14 + monocytes or THP-1 cells with LPS or LPS + soluble human IgG (sIgG) and TNF-α transcription and production, assessed RT-qPCR, ELISA, or flow cytometry, was enhanced by 30% upon LPS + sIgG compared to LPS stimulation. LPS + sIgG co-stimulation affected the NF-κB pathway (p65 phosphorylation and nucleus translocation, and IkB- α degradation). The biochemical inhibition of IRAK 1/4 and Syk kinases suppressed the enhancer effect of LPS + sIgG on TNF- α production, suggesting the involvement of both MyD88 dependent and independent pathways. Our results suggest that during LPS activation, sIgG may participate in a TLR4 - Fc-γR crosstalk.