Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells. Issue 4 (22nd January 2021)

• Record Type: Journal Article
• Authors: Cohen‐Kedar, Sarit; Keizer, Danielle; Schwartz, Suzana; Rabinowitz, Keren M.; Kaboub, Kawsar; Shaham Barda, Efrat; Sadot, Eran; Wolff‐Bar, Meirav; Shaltiel, Tali; Dotan, Iris
• Is Part Of: European journal of immunology. Volume 51:Issue 4(2021)
• Page Start: 864
• Page End: 878
• Publication Date: 2021-01-22
• Subjects: Intestinal epithelial cells -- Candida albicans -- Commensal fungi -- Cytokine secretion -- Mucosal immunity; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048852
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that β‐glucans, major fungal cell‐wall glycans, induced chemokine secretion by IEC lines in a Dectin‐1‐ and Syk‐dependent manner. Here, we show that in contrast to β‐glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL‐8, CCL2, CXCL1, and GM‐CSF. Commensal fungi and β‐glucans activated Syk and ERK in IEC lines. However, only β‐glucans activated p38, JNK, and the transcription factors NF‐κB p65 and c‐JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with β‐glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with β‐glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines. Lack of cytokine secretion in response to commensal fungi may reflect IECs' response to fungal glycans, other than β‐glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation. Abstract : Recognition of commensal fungi and β‐glucans by intestinal epithelial cells via Dectin‐1 involves activation of Syk and ERK. However, only β‐glucans stimulate secretion of proinflammatory cytokines. Inhibition of cytokine secretion upon sensing commensal fungi reflects homeostasis and may result from simultaneous tolerogenic signals activated upon glycan recognition by other receptors.