Microbiota milieu and mechanisms of intestinal Toll Like Receptors (TLRs) involved in chemotherapy induced mucositis

Abstract

Gut is not only of digestive but also of immunological importance because of the residing microbiota milieu. Pathological or certain therapeutic condition may modify the normal commensal microflora. Mucositis, the most common untoward effect of chemotherapy, can also lead to this microbiotic imbalance. This shift leads to various molecular cascades which in turn trigger the action of Pattern Recognition Receptors (PRR’s). Toll like receptor (TLR) is one such pattern recognition receptor. In the human body there are about 13 types of TLRs out of which TLR-2, TLR-4, TLR-5 and TLR-9 are intestinal specific. They respond through ligands such as bacterial derivatives like flagellin, Lipoteichoic acid, Lipopolysaccharides, microbial antigen or genetic material of the viru. In turn via adaptor molecules, TLRs alter the signalling mechanisms and further induct the activation of pro or anti-inflammatory cytokines based on the immunological need. Several of the studies have described the involvement of under twined mechanisms of TLRs during chemotherapy. Therefore, agonists and/or antagonists of these strategic molecules may play a key role in pathological and therapeutic aspects. Thus, this review is an attempt to focus on the involvement of TLRs and microbiota to different chemotherapeutic agents and thereby track the available mechanisms of functionality.