Abstract
There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.
Highlights
Probiotics have been shown to both augment/modulate homeostatic immune defences and to ameliorate specific infectious, inflammatory and allergic diseases by modulating gut function.Probiotics are described as “Live microorganisms, which, when consumed in adequate amounts, confer a health benefit on the host” by the Food and Agricultural Organization of the United Nations and the World Health Organization [1]
In the context of gut homeostasis, there is a fine balance between epithelial cell proliferation, differentiation and apoptosis, allowing this dynamic cellular barrier to continually replace itself, protect from infectious pathogenic agents and to die off prior to cellular transformation resulting from long-term exposure to carcinogenic agents present in intestinal/digesta-associated water
Probiotics have been used to treat a range of health conditions encompassing intestinal and extraintestinal sites, including atopic dermatitis, necrotising enterocolitis, pouchitis and ulcerative colitis [142,143,144]
Summary
Probiotics have been shown to both augment/modulate homeostatic immune defences and to ameliorate specific infectious, inflammatory and allergic diseases by modulating gut function. They are generally lactic acid bacteria (LAB), most commonly lactobacilli and bifidobacteria species, lactococcus, streptococcus and enterococcus species, as well as some non-pathogenic Escherichia coli strains are known probiotics [2] These probiotics have numerous effects on the gastrointestinal tract (GIT) and the gut-associated lymphoid tissue (GALT) where they modulate intestinal function and immune responses via augmentation of activation (adjuvanticity), and regulation/tolerisation (reviewed in [3]). These effects include the competitive exclusion of pathogens at the intestinal barrier, modulation of dendritic cell (DC) function, influencing T cell polarization and suppression of intestinal inflammation. The ways in which probiotics are recognised by innate immune receptors will be explored, with a particular emphasis on pathogen sensing, barrier integrity, anti-microbial and innate immune responses driven by intestinal epithelial cells (IECs) and the immune cells underneath this barrier such as the DCs, MΦs, neutrophils (NΦs) and natural killer cells (NKs)
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