Antibody ligation of CEACAM1, CEACAM3, and CEACAM6, differentially enhance the cytokine release of human neutrophils in responses to Candida albicans

• Published in: Cellular immunology 2022-01, Vol.371, p.104459-104459, Article 104459
• Main Authors: Klaile, Esther, Prada Salcedo, Juan P., Klassert, Tilman E., Besemer, Matthias, Bothe, Anne-Katrin, Durotin, Adrian, Müller, Mario M., Schmitt, Verena, Luther, Christian H., Dittrich, Marcus, Singer, Bernhard B., Dandekar, Thomas, Slevogt, Hortense
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Antibody treatment; Antigens, CD - immunology; Apoptosis - immunology; Candida albicans; Candida albicans - immunology; Candidiasis, Invasive - mortality; Candidiasis, Invasive - pathology; Carcinoembryonic Antigen - immunology; Carcinoembryonic antigen-related cell adhesion molecule; CEACAM1; CEACAM3; CEACAM6; Cell Adhesion Molecules - immunology; CXCL8; Cytokine; Cytokines - immunology; Female; GPI-Linked Proteins - immunology; Humans; Immunomodulation - immunology; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Male; Neutrophil; Neutrophils - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2021.104459

[Display omitted] •Anti-CEACAM antibodies increase the human neutrophil response to Candida albicans.•Enhanced Candida-induced CXCL8-secretion by anti-CEACAM6 and anti-CEACAM1 antibody.•Altered transcriptional response to Candida by anti-CEACAM6 and anti-CEACAM1 antibody.•Increased Candida-induced apoptosis by anti-CEACAM6 antibody.•Higher IL-6/IL1β de novo production by anti-CEACAM6 and anti-CEACAM3 antibody. Invasive candidiasis is a healthcare-associated fungal infection with a high mortality rate. Neutrophils, the first line of defense during fungal infections, express the immunoregulatory Candida albicans receptors CEACAM1, CEACAM3, and CEACAM6. We analyzed the effects of specific antibodies on C. albicans-induced neutrophil responses. CEACAM6 ligation by 1H7-4B and to some extent CEACAM1 ligation by B3-17, but not CEACAM3 ligation by 308/3-3, resulted in the immediate release of stored CXCL8 and altered transcriptional responses of the C. albicans-stimulated neutrophils. Integrated network analyses and dynamic simulations of signaling cascades predicted alterations in apoptosis and cytokine secretion. We verified that CEACAM6 ligation enhanced Candida-induced neutrophil apoptosis and increased long-term IL-1β/IL-6 release in responses to C. albicans. CEACAM3 ligation, but not CEACAM1 ligation, increased the long-term release of pro-inflammatory IL-1β/IL-6. Taken together, we demonstrated for the first time that ligation of CEACAM receptors differentially affects the regulation of C. albicans-induced immune functions in human neutrophils.