# Paneth Cell, Gut Microbiota Dysbiosis and Diabetes Mellitus
## 3 Innate Immunity of the Small Intestine
### Intestinal Epithelial Cells and Innate Immunity
#### 3.1.1 The Role of Paneth Cells in the Innate Immunity of the Small Intestine
Human \(\alpha\)-defensin 6 does not have anti-microbiocidal activity but is able to create nanonets around pathogens, thus trapping and containing them [84] (Figure 3). Figure 1: Schematic diagram showing the localisation of matured Paneth cells at the base of the intestinal crypt and higher concentration of antimicrobial peptides at the stem cell zone. The sketch also includes cells in the lamina propria that interact with the Paneth cells to support and regulate activities of the Lgr5\({}^{+}\) ISCs (created using BioRender.com accessed on the 25 April 2023). Lysozyme and IgA, also secreted by the Paneth cells, add to the antimicrobial activities in the lumen of the small intestine [80]. The other functions of the Paneth cells that are critical for the maintenance of robust innate immunity in the small intestine include the regulation of proliferation and differentiation of the LgF5+ ISCs, metabolic support of the Lgr5+ ISCs and liaison with cells involved in adaptive immunity [2; 12; 59; 60; 62; 83; 85; 86]. Abnormality in the number or function of Paneth cells is seen in numerous diseases, including viral infections [80], necrotising enterocolitis [76], prolonged use of total parental nutrition [87], starvation [88], [PERSON]'s disease [15; 77; 83; 89; 90; 91], smoking [90] and ageing [8]. A change in the total number of Paneth cells or a deterioration in the quality of their function may also occur during chronic HIV infections [92]. 1.2 Absorptive Enterocytes, Goblet Cells, Tuft Cells, M-Cells and Junctional and Innate Immunity of the Small Intestine  
Goblet cells augment the antimicrobial defence by secreting mucous made up of mucins, water and trefoil factors. MUC2 is the major constituent of the mucus and helps to form a carpet of mucus that maintains a higher concentration of antimicrobial peptides in the area adjacent to the surface of the IECs [74]. Secretory mucus is an essential nutrient for some commensal organisms. The absorptive enterocytes are the most abundant IECs [2]. Figure 2: Schematic diagram depicting the mechanism of stimulation and some of the substances that are secreted by the Paneth cell (created using BioRender.com 9 of April 2023). LPS = lipopolysaccharide,CNS = central nervous system, Notch = neurogenic locus notch homolog protein 2, EGF = epidermal growth factor, IgA = IgA immunoglobulin, TNF = tumour necrosis factor, Wnt = wingless/integrated. Absorptive enterocytes have pathogen recognition receptors, which they use to sample the contents in the lumen of the small intestine and therefore participate in innate gut defence [9]. Like any other epithelial cell throughout the body, the absorptive enterocytes secrete \(\beta\)-defensin and not HD-5 or HD-6. Other IECs that participate in the regulation of the microbiota in the lumen of the small intestine are the tuft cells and the M-cells [58; 93; 94; 95; 96]. The tuft cells sample the gut microbiota like the Paneth cells but to a limited extent [96; 97; 98]. Secretions from the tuft cells are limited to cytokines [99]. Tuft cells have not been shown to secrete antimicrobial peptides, growth factors or catecholamines [99]. The junctional proteins also add to the innate immunity of the small intestine [5; 7; 27].