Role of Toll-like receptors in the modulation of intestinal inflammation by immunobiotics

JULIO VILLENA; HARUKI KITAZAWA

Probiotics: Immunobiotics and Immunogenics

CRC Press

Año: 2013;

Innate immune receptors that recognize conserved components derived from microbes are widely expressed by both IECs and DCs of the gastrointestinal tract and play a key role in intestinal homeostasis and host protection from infectious pathogens. However, aberrant innate immune activation through these receptors may also drive intestinal pathology, and therefore, a balanced interaction between the microbiota and innate immune activation is required to maintain a healthy mutualistic relationship between the microbiota and the host. How pathogenic and commensal microbes are distinguished by IECs and DCs of the gastrointestinal tract is not completely understood. As reviewed in this chapter, TLRs seem to play a crucial role in both intestinal homeostasis and defenses. Several reports have demonstrated that immunobiotic strains can be used to regulate immune responses in the gut to improve defenses and avoid the loss of equilibrium between finely tuned pro- and anti-inflammatory mechanisms in the gastrointestinal tract. Specific MAMPs or effector molecules have been identified in the last few years that may be linked to certain immune modulatory capacities of lactobacilli in vitro, using host cell line-based assays, as well as in vivo, mainly using mouse models. The data summarized in this chapter highlight the role of TLRs in this innate immune regulation induced by immunobiotics. In this sense, our studies demonstrated that previous interactions of immunobiotic strains with porcine IECs or APCs significantly modulate the response of these cells to a challenge with TLRs agonists. These modifications induced by immunobiotics in epithelial and immune cells may contribute to intestinal immune homeostasis by ensuring that the contact of IECs or APCs with microbial products does not automatically result in the generation of a potentially destructive inflammatory response. Performing detailed studies of the changes in signaling pathways in IECs and APCs produced by the interaction of immunobiotics with PRRs and in particular with TLR2 will be of great importance. Another interesting point for future investigations is the influence of immunobiotics on the interaction of IECs and DCs and the subsequent generation of Treg cells. In this sense, our porcine cell culture systems may be of great help as human models. The influence of immunobiotics on both PRR signaling pathways in IECs and on IEC–DC interactions is currently under investigation in our laboratory using these porcine systems. Ultimately, a better understanding of the host-microbe interactions in the gut will provide new opportunities for the prevention and treatment of a number of inflammatory disorders using immunobiotic strains. Moreover, the studies reviewed here direct us towards the concept of more personalized application of immunobiotics to improve their efficacy, depending on the specific disorders. Detailed molecular comprehension should ultimately lead to a more focused and rational application of immunobiotics in functional foods or feeds.