Crosstalk is the term used for designing the interaction between host cells and microbes. Among other mechanisms, this takes place when certain molecules of the microorganisms are recognized by the toll-like receptors (TLRs) in the body cells, mainly at the mucosal level. 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 (Ospelt, C., et al. Int. J. Biochem. Cell Biol. 2010, 42, 495–505).
Several in vitro, in vivo and clinical approaches have demonstrated that components present in the diet, are able to modulate TLR-mediated signaling pathways (Pérez-Cano, F., et al. Antioxidants 2014, 3, 649–670). Among these dietary factors, we can find polyphenols, and, in this context, certain studies have demonstrated how cocoa, as a rich source of flavonoids, is able to modify this type of interaction. In particular, cocoa flavonoids and cocoa fiber have shown their ability to modify the composition of the microbiota and to modulate TLR gene expression (Massot-Cladera, M., et al. Arch. Biochem. Biophys. 2012, 527, 105–112; Massot-Cladera, M., et al. Br. J. Nutr. 2014, 112, 1944–1954; Massot-Cladera, M., et al. J. Funct. Foods 2015, 19, 341–352).
Moreover, flavonoids present in cocoa have demonstrated the ability to regulate the downstream signaling molecules involved in the TLR pathway. Due to this modulatory action, among others, cocoa influences the immune system, particularly the inflammatory innate response and the systemic and intestinal adaptive immune response.
To date, a cocoa diet is able to modulate pro-inflammatory cytokines, to change the lymphocyte composition and functionality of adaptive response (by means of inhibiting Th2 cell function) and to change innate immunity (potentiating certain aspects of mucosal Natural Killer response).
However, further research should be directed to elucidate the cocoa compounds involved in such effects and also the possible medical approaches to these impacts (Pérez-Cano, F.J., et al. Front. Pharmacol. 2013, 4, 71).
Overall, although the molecular targets involved in the modulatory action of cocoa on TLR-mediated signaling pathways, and its consequences, are not fully understood, some synergistic mechanisms of cocoa compounds are suggested for the preventive effect on certain inflammatory, immune-mediated or chronic diseases.
Acknowledgments: Grants AGL2008-02790 and AGL2011-24279 from the Spanish Ministry of Science and Innovation and the Ministry of Economy and Competitiveness, respectively.