A balance between tissue-destructive and tissue-protective immunities: A role of toll-like receptors in regulation of adaptive immunity

The immune system has been shown to be involved in not only the host defense against infectious pathogens but also in tissue repair processes continuously occurring in the body. Our review presents the hypothesis about the mechanism of TLR-mediated regulation of adaptive immune responses linked to the tissue destruction. In our opinion following injury to a tissue, the expression of tissue-specific determinant/MHC class II complexes on dendritic cells and macrophages are upregulated significantly due to the increased uptake of tissue debris. Consequently, T-cells become activated as a result of low affinity, but high avidity interactions between self-reactive CD4(+) T cells and antigen-presenting cells (APCs). The type of self antigen-induced immune responses depends on the multiple downstream signals generated by intracellular toll-like receptors (TLRs) 3, 7, 8, and 9, that discriminate self and non-self nucleic acids. Accumulating data suggest that ligation of intracellular TLRs by endogenous DNA/RNA released from necrotic cells may result in developing Th2-like responses, as well as in the alternative activation of macrophages (M2), that favor local tissue protection and compensatory cell growth. In contrast, ligation of intracellular TLRs by exogenous pathogen-derived DNA/RNA may promote Th1-driven responses, as well as classical activation of macrophages (M1), that contribute to local tissue destruction and suppress cell growth. We suggest here that the balance between the host- and pathogen-derived nucleic acids interacting with intracellular TLRs contributes to the balance between immune-mediated tissue-protective and tissue-destructive events occurring in the body. (C) 2011 Elsevier GmbH. All rights reserved.