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The gut mucosal immune system

The intestinal mucosa is the largest body-surface to the external environment. The mucosa is exposed to a massive number of antigens derived from the intestinal microbiome and from the diet.1 To be able to cope with this amount of antigens, 70% of the body’s entire immune system is located in the gut.2 The gut mucosal immune system must maintain tolerance towards benign microbiome and dietary antigens and at the same time be able to elicit appropriate immune responses to pathogens.3 Consequently, the intestinal mucosa is constantly under immune surveillance. Three mucosal lymphoid structures define the intestinal immune system: Peyer’s patches, the lamina propria and the epithelium.4 Peyer’s patches are large lymphoid structures scattered along the intestines. They contain diverse immune cells such as T and B lymphocytes, macrophages and dendritic cells (DCs).3

In addition to the high abundance of DCs in Peyer’s patches, DCs can open the tight junctions between epithelial cells, send dendrites outside the epithelium and directly sample the intestinal lumen.5
DCs are one type of antigen presenting cells and they are important for the surveillance of the intestinal mucosal environment. When DCs sample antigens they are activated and the activated DCs then present the antigen to naive T-helper cells to prime these. Depending on the cue provided by the DCs, T-helper cells may develop into T-regulatory (Treg) cells leading to tolerance, or T-helper cells that initiates inflammatory cascades.6, 7 Due to their ability to sense and integrate signals from their local environment DCs are central to the maintenance of tolerance and the mounting of immune responses when needed.7

Depending on the priming, T-helper cells will start secreting cytokines with different signaling functions. A major anti-inflammatory cytokine secreted by Tregs is interleukin-10 (IL-10). IL-10 is important for immune regulation and suppressing the inflammatory response, and thus for the maintenance of immune homeostasis.1, 8 Other cytokines such as IL-1β, IL-6, and TNF-α are important for activating the immune system.9
If bacterial, viral, fungal, or parasitic pathogens invade the gut mucosa an appropriate immune response is required to eliminate the intruders. When receptors on DCs sample pathogen-associated molecular patterns (PAMPs), the DCs will secrete chemokines and cytokines that promotes expansion of the pro-inflammatory T-helper cell subsets, Th1, Th2, or Th17,10, 11 which subsequently stimulates and attracts a variety of effector immune cells (cytotoxic T cells, macrophages, and antibody producing B cells) that combat the infection.12, 13 This diversity of immunity ensures that tailored and maximally protective responses can be mounted against the variety of pathogenic microorganisms which may be present in the gut.14 

Acute inflammation is characterized by a quick onset of inflammation followed by resolution and return to homeostasis.15, 16 Persistent inflammatory stimuli or incomplete resolution of inflammation results in chronic inflammation.17 Chronic inflammation is an underlying factor in a range of diseases, such as inflammatory bowel disease (IBD),18 atherosclerosis,19 arthritis,20 and neurodegenerative diseases such as Alzheimer’s disease.21

The effects of probiotics on the immune system and their mechanisms of action varies between different probiotic strains.11 High-quality studies suggest that Lactobacillus rhamnosus, LGG®, Lactobacillus paracasei, L. CASEI 431® and Bifidobacterium, BB-12® strains may support the immune system, and are thus associated with reduced incidence, duration and severity of respiratory issues in children and adults.22, 23, 24, 25, 26 Data suggest that the strains help trigger a Th1-mediated immune response, both by stimulating INF-γ to induce the maturation of Th1 cells, and by stimulating secretion of proteins such as IL-12, IL-2 and IL-6 cytokines. These are needed for further inducing the production of antibodies that are required to fight invading pathogens.27, 28, 29, 30, 31, 32

LGG®, L. CASEI 431®, and BB-12® are registered trademarks of Chr. Hansen A/S.

The article is provided for informational purposes regarding probiotics and is not meant to suggest that any substance referenced in the article is intended to diagnose, cure, mitigate, treat, or prevent any disease.

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References Open Close

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