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Frontiers in Immunology 2023The gut is a crucial organ in insect defense against various pathogens and harmful substances in their environment and diet. Distinct insect gut compartments possess... (Review)
Review
The gut is a crucial organ in insect defense against various pathogens and harmful substances in their environment and diet. Distinct insect gut compartments possess unique functionalities contributing to their physiological processes, including immunity. The insect gut's cellular composition is vital for cellular and humoral immunity. The peritrophic membrane, mucus layer, lumen, microvilli, and various gut cells provide essential support for activating and regulating immune defense mechanisms. These components also secrete molecules and enzymes that are imperative in physiological activities. Additionally, the gut microbiota initiates various signaling pathways and produces vitamins and minerals that help maintain gut homeostasis. Distinct immune signaling pathways are activated within the gut when insects ingest pathogens or hazardous materials. The pathway induced depends on the infection or pathogen type; include immune deficiency (imd), Toll, JAK/STAT, Duox-ROS, and JNK/FOXO regulatory pathways. These pathways produce different antimicrobial peptides (AMPs) and maintain gut homeostasis. Furthermore, various signaling mechanisms within gut cells regulate insect gut recovery following infection. Although some questions regarding insect gut immunity in different species require additional study, this review provides insights into the insect gut's structure and composition, commensal microorganism roles in and life cycles, different signaling pathways involved in gut immune systems, and the insect gut post-infection recovery through various signaling mechanisms.
Topics: Animals; Drosophila melanogaster; Signal Transduction; Homeostasis; Antimicrobial Peptides; Insecta
PubMed: 38193088
DOI: 10.3389/fimmu.2023.1272143 -
Frontiers in Immunology 2023T cell activation is initiated by the recognition of specific antigenic peptides and subsequently accomplished by complex signaling cascades. These aspects have been... (Review)
Review
T cell activation is initiated by the recognition of specific antigenic peptides and subsequently accomplished by complex signaling cascades. These aspects have been extensively studied for decades as pivotal factors in the establishment of adaptive immunity. However, how receptors or signaling molecules are organized in the resting state prior to encountering antigens has received less attention. Recent advancements in super-resolution microscopy techniques have revealed topographically controlled pre-formed organization of key molecules involved in antigen recognition and signal transduction on microvillar projections of T cells before activation and substantial effort has been dedicated to characterizing the topological structure of resting T cells over the past decade. This review will summarize our current understanding of how key surface receptors are pre-organized on the T-cell plasma membrane and discuss the potential role of these receptors, which are preassembled prior to ligand binding in the early activation events of T cells.
Topics: T-Lymphocytes; Signal Transduction; Cell Membrane; Leukocyte Common Antigens; Cell Communication; Antigens
PubMed: 37795089
DOI: 10.3389/fimmu.2023.1264721 -
Rheumatology (Oxford, England) Aug 2023In SSc, gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota...
OBJECTIVES
In SSc, gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling.
METHODS
We analysed duodenal biopsies obtained pre-intervention (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving an intestinal infusion of FMT (n = 5) or placebo (n = 4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling.
RESULTS
In patients receiving FMT, the number of podoplanin- and CD64-expressing cells in the mucosa were lower at week 2 compared with baseline. This decline in podoplanin- (r = 0.94) and CD64-positive (r = 0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T cell receptor complexes, and chemokine receptors, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16.
CONCLUSION
Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement.
TRIAL REGISTRATION
ClinicalTrials.gov, http://clinicaltrials.gov, NCT03444220.
Topics: Humans; Fecal Microbiota Transplantation; Double-Blind Method; Intestines; Intestinal Mucosa; Scleroderma, Systemic; Treatment Outcome
PubMed: 36688692
DOI: 10.1093/rheumatology/kead014 -
EMBO Reports Oct 2023Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the...
Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5-deficient mice. The defects result in severe mucosal damage after exposure to the colitis-inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5-deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single-cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease.
PubMed: 37691494
DOI: 10.15252/embr.202357084