Cytokines regulate complement receptor immunoglobulin expression and phagocytosis of Candida albicans in human macrophages: A control point in anti-microbial immunity

• Published in: Scientific reports Vol. 7; no. 1; pp. 4050 - 16
• Main Authors: Munawara, Usma, Small, Annabelle G., Quach, Alex, Gorgani, Nick N., Abbott, Catherine A., Ferrante, Antonio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/21; 631/250/254; 631/250/256/2515; 82; 82/29; Candida albicans; Candida albicans - immunology; Candidiasis - etiology; Candidiasis - metabolism; Colony-stimulating factor; Complement receptors; Cytokines; Cytokines - metabolism; Cytokines - pharmacology; Gene Expression; Granulocyte-macrophage colony-stimulating factor; Humanities and Social Sciences; Humans; Immunoglobulins; Inflammation Mediators; Innate immunity; Integrin alphaXbeta2 - genetics; Interferon; Interleukin 10; Interleukin 13; Interleukin 6; Lymphotoxin; Macrophage colony-stimulating factor; Macrophage-1 Antigen - genetics; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Monocytes; multidisciplinary; Phagocytosis; Phagocytosis - drug effects; Phagocytosis - immunology; Receptor mechanisms; Receptors, Complement - genetics; Receptors, Complement - immunology; Science; Science (multidisciplinary); Transcription; Transforming growth factor; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-04325-0

Complement Receptor Immunoglobulin (CRIg), selectively expressed by macrophages, plays an important role in innate immunity by promoting phagocytosis of bacteria. Thus modulation of CRIg on macrophages by cytokines can be an important mechanism by which cytokines regulate anti-microbial immunity. The effects of the cytokines, tumor necrosis factor, transforming growth factor-β1, interferon-γ, interleukin (IL)-4, IL-13, IL-10, IL-1β, IL-6, lymphotoxin-α, macrophage-colony stimulating factor (M-CSF) and GM-CSF on CRIg expression were examined in human macrophages. We demonstrated that cytokines regulated the CRIg expression on macrophages during their development from monocytes in culture at the transcriptional level using qPCR and protein by Western blotting. Both CRIg spliced forms (Long and Short), were similarly regulated by cytokines. Direct addition of cytokines to matured CRIg+ macrophages also changed CRIg mRNA expression, suggesting that cytokines control macrophage function via CRIg, at two checkpoints. Interestingly the classical complement receptors, CR3 and CR4 were differentially regulated by cytokines. The changes in CRIg but not CR3/CR4 mRNA expression correlated with ability to phagocytose
Candida albicans
by macrophages. These findings suggest that CRIg is likely to be a control point in infection and immunity through which cytokines can mediate their effects, and is differentially regulated from CR3 and CR4 by cytokines.