Host discriminates between probiotics and pathogens: impact of toll like receptor 5-flagellin interaction and evolution

Abstract:

[Objective] Data from ample studies support the idea that the immune homeostasis is crucially dependent on a cross-talk between host immune system and enteric flora in which the host recognizes and responses distinctively to probiotic and pathogenic bacteria. The toll-like receptors (TLRs) and microorganism associated molecular patterns (MAMPs) may play a major role in the host discrimination between probiotics and pathogens, as the recognition of MAMPs by TLRs can activate innate immune response and prime the adaptive immune system. In the TLRs family, TLR5 that responds to flagellin is the only protein-binding TLR, it’s much easier to study the flagellin-TLR5 interaction structurally and functionally. The overall aim of this study was to test for a possible contribution of the flagellin-TLR5 crosstalk to the host discrimination between probiotic and pathogenic bacteria. [Methods] Using flagellin protein sequences from probiotic and pathogenic bacteria living in gastrointestinal tract, we firstly constructed a phylogenetic tree of flagellin proteins and then aligned the flagellin protein sequences in TLR5 recognition region between probiotic and pathogenic bacteria. [Results] We found that probiotic and pathogenic bacteria differed in flagellin protein sequence, particularly in the TLR5 recognition sites. [Conclusion] Acclimatization to TLR5 recognition may result in the different TLR5 recognition sites on flagellin between pathogens and probiotics. Moreover, previous studies show that stimulation of basolaterally expressed TLRs results in inflammatory response, but activation of apically expressed TLRs leads to inhibition of the proinflammatory response. Altogether, our findings provide preliminary but encouraging evidence for the existence of crosstalk between flagellin and TLR5 which may be one of the mechanisms for the host discrimination between probiotics and pathogens.