Mast cells at the crossroads of microbiota and IBD

Abstract

The human gut harbors a wide range of microorganisms that play a fundamental role in the well-being of their host. A dysregulation of the microbial composition can lead to the development or exacerbation of gastrointestinal (GI) disorders. Emerging evidence supports the hypothesis that mast cells (MCs) play a role in host-microbiota communication, modulating the mutual influence between the host and its microbiota through changes in their activation state. The ability of some bacteria to specifically affect MC functions and activation has been extensively studied, with different and sometimes conflicting results, while only little is known about MC-fungi interactions. In this review, the most recent advances in the field of MC-bacteria and MC-fungi interactions will be discussed, with a particular focus on the role of these interactions in the onset of GI disorders such as inflammatory bowel diseases (IBD). Moreover, the connection between some MC-targeting drugs and IBD was discussed, suggesting probiotics as reasonable and promising therapy in the management of IBD patients. Keywords: Inflammatory bowel disease (IBD) r Intestine r Mast cells r Microbiota r Neurons Additional supporting information may be found online in the Supporting Information section at the end of the article. of the high affinity receptor for IgE on the surface of the cell and of the proteases-containing granules in the cytosol, under the influence of tissue-specific molecules (including SCF, IL-3, and IL-9) and bacterial-derived molecules (LPS and peptidoglycan) present in the local microenvironment [1]. Intestinal homing of MCs progenitors is mainly mediated by the interaction of α4β7 integrin expressed by MCs with ICAM-1, V-CAM, or MAdCAM-1 expressed by endothelial cells and it is influenced by CXCR2 ligation [2, 3].MCs possess a great number of costimulatory molecules, including members of the B7 family (ICOSL, PD-L1, and PD-L2,) and of the TNF/TNFR families (OX40L, CD153, Fas, 4-1BB, and glucocorticoid-induced TNFR), which allow them to interact with different partners both from immune and nonimmune cells populations as well as with bacteria and fungi through the expression of different pattern-recognition receptors (PRRs) [4]. Moreover, MCs harbor a high number of cytoplasmic granules that contain preformed immunomodulatory compounds such as proteases, histamine, heparin, and TNF-α. Given the wide pattern Eur.

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta‐analysis

“…Remarkably, there is increasing evidence describing the role of gut microbiota in the activation of mast cells, in addition to its involvement in amplifying IgE-and non-IgE-mediated allergies. 54,55 Psychiatric comorbidities and psychosocial stress are also common in IBS. However, the exact pathogenesis through which psychological stressors induce symptoms in IBS remains to be elucidated.…”

Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells

“…Accumulating evidences indicated that the function of MCs in IBD is more complicated than originally thought, Animal and human clinical studies suggested that the contribution of these cells includes regulating epithelium permeability, immune signal transmittance, maintenance and resolution of inflammatory responses, and subsequent tissue remodeling [2,[30][31][32][33][34]. What's more, the study showed that the increase of MCs infiltration near the epithelium resulted in a favorable microenvironment that expressed more beneficial proteins including ZO-1, FGF2, ANGPTL2, REG3γ, and REG3β, which are involved in signal transduction, cell growth, tissue repair, and homeostasis maintenance [2].…”

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…These cells can be involved in several autoimmune disorders, such as rheumatoid arthritis [37], coeliac disease [94], multiple sclerosis [124], and bullous dermatoses [125]. Mast cell-nerve communications are involved in stress, pain, pruritus [126,127], and in inflammatory bowel diseases [35,36].…”

“…Moreover, these cells can be activated by different viral [25,26] and bacterial proteins [27,28] and thereby represent a potentially important cell during microbial infections. Therefore, the spectrum of diseases in which mast cells and their mediators have been implicated has extended to include bacterial, fungal, viral, and helminth infections [26,[29][30][31]; several diseases of the cardiovascular [14,32,33] and gastrointestinal systems [34][35][36]; and the joints [37,38]. Figure 1 schematically summarizes the wide spectrum of pathophysiological conditions in which mast cells and their mediators have been implicated during the last decades.…”