Induction of intercrypt goblet cells upon bacterial infection
Authors: Léonard Renaud , Pasquereau-Kotula Ewa , Madec Edwige , Marsac Benjamin , Mihalache Adriana , du Merle Laurence , Denis Jordan , Spriet Corentin , Sansonetti Philippe , Dramsi Shaynoor , Masselot Catherine Robbe 
Published: July 2024

SummaryIntestinal mucins play a crucial role in the mucosal barrier, serving as the body’s initial defense against microorganisms. However, how the host regulates the secretion and glycosylation of these mucins in response to bacterial invasion remains unclear. Our study demonstrates that when exposed toStreptococcus gallolyticus(SGG), a gut pathobiont, the host mucosa promptly adjusts the behavior of specialized goblet cells (GCs) located in the middle of the crypts. A subset of these cells undergoes a transformation, becoming intercrypt goblet cells (icGCs), which do not detach from the surface but instead migrate along intercrypt spaces while secreting mucins. These mucins form a dense layer covering the epithelial cell surface and filling the gaps between mucus plumes secreted from crypt openings, thereby forming a continuous protective mucus layer. Notably, the mucins produced by icGCs exhibit a distinct glycosylation pattern that makes them impermeable to bacterial pathogens. Significantly, a non-piliatedSGGmutant unable to bind to mucus fail to induce icGCs, allowing its translocation through the mucosa and submucosa. Intriguingly, a closely related mucus-adherent bacterium,SGM, which is considered non-pathogenic, also triggers the differentiation of GCs into icGCs. This discovery opens new avenues for treating patients with intestinal diseases characterized by mucus layer deficiencies, such as inflammatory bowel diseases and metabolic disorders. Utilizing mucus-adherent probiotics to induce icGCs represents a promising strategy for reinforcing the mucosal barrier.Graphical abstractIn briefWe demonstrate here that, upon oral infection by a gut pathobiont, namelyStreptococcus gallolyticus, the murine intestinal mucosa displays a novel type of goblet cells recently described as intercrypt goblet cells (icGCs). These icGCs are not shed at the surface of epithelial cells, in contrast to differentiated goblet cells, and produce a continuous protective mucus layer, with a specific pattern of glycosylation rendering it impenetrable to bacteria. No icGCs were induced in response to a non-mucus bindingSGGmutant, thus allowing bacterial translocation into the mucosa and submucosa, highlighting the essential role played by icGCs in the protective mucus barrier function. Importantly,SGM, a commensal mucus-adherent bacterium recognized as safe, is also able to stimulate production of icGCs, opening avenues in the treatment of patients with a “leaky gut”.HighlightsInduction of intercrypt goblet cells in murine intestinal tract upon bacterial infectionicGC potentially arise from differentiated goblet cells through cellular plasticityMucus produced by icGCs is critical for host defense and mucosal barrier functionCommensal mucus-adherent bacteria also induce icGCs, paving the way for new probiotic treatments for strengthening the mucosal barrier of patients with inflammatory bowel diseases and metabolic disorders