Abstract
Interaction between host cells and microbes is known as crosstalk. Among other mechanisms, this takes place when certain molecules of the micro-organisms are recognized by the toll-like receptors (TLRs) in the body cells, mainly in the intestinal epithelial cells and in the immune cells. TLRs belong to the pattern-recognition receptors and represent the first line of defense against pathogens, playing a pivotal role in both innate and adaptive immunity. Dysregulation in the activity of such receptors can lead to the development of chronic and severe inflammation as well as immunological disorders. Among components present in the diet, flavonoids have been suggested as antioxidant dietary factors able to modulate TLR-mediated signaling pathways. This review focuses on the molecular targets involved in the modulatory action of flavonoids on TLR-mediated signaling pathways, providing an overview of the mechanisms involved in such action. Particular flavonoids have been able to modify the composition of the microbiota, to modulate TLR gene and protein expression, and to regulate the downstream signaling molecules involved in the TLR pathway. These synergistic mechanisms suggest the role of some flavonoids in the preventive effect on certain chronic diseases.
Highlights
Interaction between host cells and microbes is known as crosstalk
As the activation of the toll-like receptors (TLRs) pathway constitutes the first step in the inflammatory cascade activation, and its deregulation can lead to severe chronic inflammation and immune disorders, it is plausible to hypothesize a downmodulatory action of flavonoids in the TLR-induced pathways
The activation of TLR intracellular signaling activation requires further processes that can be targeted by flavonoids. These processes include the accumulation of lipid rafts, microdomains rich in cholesterol and sphingolipids that act as platforms for downstream molecules and seem to be a key factor in the activation of immune cells, TLR dimerization/oligomerization [74], its glycosilation and the participation of adaptor proteins
Summary
The intestinal mucosa is constantly interacting with a high load of antigens, which comprises, besides those from food, those derived from microbes, both commensal microbiota and invading pathogens. Certain microbiota components can be recognized through the pattern-recognition receptors (PRRs) These are host innate immune receptors involved in the detection of pathogens that recognize conserved molecular structures known as pathogen-associated molecular patterns (PAMPs) as well as microbe-associated molecular patterns (MAMPs) (host-commensal interactions) and induce the production of innate effector molecules. These can be located on the cell membrane or in the cytosol joining to bacterial-surface-exposed structures or nucleic acids, respectively. Among components present in the diet, polyphenols, mainly flavonoids, have been suggested as dietary factors able to modulate TLR-mediated signaling pathways [5]
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