• Microbiome_mucosa

Itt írjon a(z) Microbiome_mucosa-ról/ről

Interaction between the gut microbial and the mucosal immune system

Introduction

The largest symbiotic ecosystem can be found in the gastrointestinal tract extending from the oral cavity to the anus. The main physiological function is the digestion of food, absorption of nutrients and elimination of waste products. The gastrointestinal tract is the entrance of viral and bacterial pathogens and imbalance in this microbiome can lead to disruption of the intestinal homeostasis. This is caused by the disproportion of the commensal and the pathogenic microbes (Li et al., 2017). The gut microbiome consists of virus, bacteria and fungi with a wide range of bacteria up to 1,500 species, however, research have shown that the individual composition of the microbial environment is affected by different environmental factors and consist of around 160 species. As a part of the mucosa-associated lymphoid tissue (MALT) the gut-associated lymphoid tissue (GALT) is an important factor in the regulation and acts as a protective barrier for the gastrointestinal tract. Important components for the protection of the gut are mucosal immune cells, immune organs, cell receptors, cytokines and Payer’s patches among with the lamina propria and epithelia. (Tokuhara et al., 2019).

Commensal vs pathogenic bacteria

Commensal bacteria are virus, fungi and bacteria that inhabit the host without causing harm, and they are part of the normal microflora with a close relationship to the host animal. They consist of microorganisms presents on epithelial-covering surfaces like the gastrointestinal tract, respiratory tract, vagina etc. The microorganism co-evolved with the host and contains components able to activate adaptive and innate immunity. However, unlimited immune activations from commensal bacteria can pose risk of inflammation. Consequently, this requires a well-regulated control mechanism for eliminating tolerating non-dangerous antigens, food, and commensal bacteria which is done by the mucosal immune system. On the other hand, the mucosal immune system must exhibit a local defense-mechanism to threats like invading pathogens and this is fulfilled by the developed innate immune system which ensures proper function of the mucosal barrier. (Tlaskalová-Hogenová et al., 2004). Pattern-recognizing receptors (PRRs) have a major role in the adaptive and innate immunity. In the group covered by PRRs, toll-like receptors (TLRs) can be found. They are expressed immune cells and some non-immune cells like the intestinal epithelium. TLRs can distinguish different pathogens based on the molecular signatures, the so-called pathogen-associated molecular pattern (PAMP). PRR signalling result in the production of different proinflammatory cytokines and interferons (Bertics et al., 2013). In the symbiosis between the microbiota and the host the TLR-based recognition is important for the regulation of immune response in the intestine.

In the intestinal lumen, the intestinal epithelial cells are the first line of defence against pathogens. The intestinal epithelial cells are composed of different cells like enterocytes, Paneth cells, plasma cells and goblet cells. These cells cooperate to maintain intestinal homeostasis and promote host defence. The cells stimulated by pathogens and other antigens can be termed immunoreactive, and the intestinal mucosal immune response is induced by the local mucosal tissues where the immunoreactive cells are found. Plasma cells located in the intestinal lamina propria produce secretory immunoglobulin A, which is the main effector of mucosal response. Secretory immunoglobulin A (sIgA) neutralize bacterial toxins in the lumen and protects the mucosal surface and by this also function to maintain the immune stability and resisting pathogens. (Peng et al., 2021)

Effector and induction site

The function of the intestinal mucosal immune system can be divided into two, the induction and effector sites by function and tissue structure. GALT is mainly the induction site, which is composed of mesenteric lymph nodes and Peyer’s patches. Peyer’s patches have microfold cells which function to shuttle antigens into the Peyer’s patches for appropriate immune response. In addition, Payer’s patches generate Ig-A producing plasma cells for T-cell responses in the gut. The induction sites also have antigen presenting cells including dendritic cells, intestinal epithelial cells and macrophages. The effector sites are found in the lamina propria and in the epithelial layer with lymphocyte cells. Antigens are presented by antigen-presenting cells to the effector cells, which result in the production of antibodies and an immune response. (Peng et al., 2021).

The sampling of commensal bacteria is a mechanism where the commensal bacteria provide colonization resistance to antigens. Special receptors allow mucosal dendritic cells to extend into the intestinal lumen to engulf bacteria. From the intestine the bacteria are transported to the mesenteric lymph nodes where they selectively induce production of IgA by plasma cells. The antibodies bind and modulate the composition of the gut microbiota which limits inflammatory response and prevents penetration of pathogenic and commensal bacteria. This sampling of commensal bacteria also induces differentiation of T-cells subsets.

Defensin

Effects of a compromised immune system on the gut microbiome

Factors affecting homeostasis of microbiota

Age and delivery pattern

Diet

Antibiotics

Methods of the gut microbiota modulation

Probiotics

Prebiotics

Faecal microbiota transplantation (FMT)

Diseases caused by gut microbiome dysbiosis

Conclusions

References

Figures