The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of commensals over pathogenic microbes. The canonical AMPs are helictical peptides that form lethal pores in microbial membranes. In higher life forms, this type of AMP is exemplified by the defensin family of AMPs. In epithelial tissues, defensins, and calprotectin (complex of S100A8 and S100A9) have evolved to work cooperatively. The mechanisms of action differ. Unlike defensins, calprotectin sequesters essential trace metals from microbes, which inhibits growth. This review focuses on defensins and calprotectin as AMPs that appear to work cooperatively to fortify the epithelial barrier against infection. The antimicrobial spectrum is broad with overlap between the two AMPs. In mice, experimental models highlight the contribution of both AMPs to candidiasis as a fungal infection and periodontitis resulting from bacterial dysbiosis. These AMPs appear to contribute to innate immunity in humans, protecting the commensal microflora and restricting the emergence of pathobionts and pathogens. A striking example in human innate immunity is that elevated serum calprotectin protects against neonatal sepsis. Calprotectin is also remarkable because of functional differences when localized in epithelial and neutrophil cytoplasm or released into the extracellular environment. In the cytoplasm, calprotectin appears to protect against invasive pathogens. Extracellularly, calprotectin can engage pathogen-recognition receptors to activate innate immune and proinflammatory mechanisms. In inflamed epithelial and other tissue spaces, calprotectin, DNA, and histones are released from degranulated neutrophils to form insoluble antimicrobial barriers termed neutrophil extracellular traps. Hence, calprotectin and other AMPs use several strategies to provide microbial control and stimulate innate immunity.
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http://dx.doi.org/10.3389/froh.2022.958480 | DOI Listing |
J Crohns Colitis
January 2025
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Background And Aims: Protein tyrosine phosphatase non-receptor type 23 (PTPN23) regulates the internalization of growth factor receptors such as the epithelial growth factor receptor (EGFR). Given the crucial function of such receptors in intestinal epithelial cells (IECs), we assessed the involvement of PTPN23 in intestinal homeostasis and epithelial proliferation.
Methods: We generated mouse models with constitutive (PTPN23fl/flVilCre+/-) or inducible (PTPN23fl/flVilCreERT+/-) deletion of PTPN23 in IEC.
Immun Inflamm Dis
January 2025
Department of Health Care, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Purpose: C9orf72 deficiency contributes to severe inflammation in mice. Ulcerative colitis (UC) is a chronic inflammatory disorder with the shortage of clinical success. However, whether C9orf72 is involved in the progression of UC is not fully understood.
View Article and Find Full Text PDFUnited European Gastroenterol J
January 2025
Department of Gastroenterology, CHU Liège, Liège, Belgium.
Background And Aims: Probe-based confocal endomicroscopy (pCLE) allows real-time microscopic visualization of the intestinal mucosa surface layers. Despite remission achieved through anti-tumor necrosis factor or vedolizumab therapy, anomalies in the intestinal epithelial barrier are observed in inflammatory bowel disease (IBD) patients. Our study aimed to assess these abnormalities in non-IBD individuals and compare them with IBD patients in endoscopic remission to identify the associated factors.
View Article and Find Full Text PDFIn Vitro Model
June 2024
In Vitro Toxicology Group, Faculty of Medicine, Health and Life Sciences, Swansea University Medical School, Swansea University, Sketty, Wales SA2 8PP UK.
Unlabelled: Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings.
View Article and Find Full Text PDFIn Vitro Model
December 2024
Institute of Applied Biotechnology, University of Applied Science Biberach, Hubertus-Liebrecht Strasse 35, 88400 Biberach, Germany.
Purpose: For optimization of respiratory drug delivery, the selection of suitable in vitro cell models plays an important role in predicting the efficacy and safety of (bio)pharmaceutics and pharmaceutical formulations. Therefore, an in-depth comparison of different primary and permanent in vitro cellular airway models was performed with a focus on selecting a suitable model for inhalative antibodies.
Methods: Primary cells isolated from the porcine trachea were compared with the established human cell lines CaLu3 and RPMI 2650.
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