Both gram-positive and gram-negative bacteria and their cell wall components activate innate immune system of the host and induce secretion of proinflammatory molecules, mainly chemokines and cytokines [1]. Toll-like receptors (TLRs) initiate signaling cascades through recognition of a variety of microbial components, thus serving as an important link between innate and adaptive immune responses. Each TLR recognizes distinct ligands [2]. TLR2 agonists include peptidoglycan, lipoproteins, and lipopeptides from Gram-positive bacteria, mycobacterial lipoarabinomannan, mycoplasma lipopeptides [3], but only when present as a heterodimer in combination with either TLR1 or TLR6 [4]. TLR3 and TLR5 mediate cell activation by double-stranded viral RNA and bacterial flagellin, respectively [3]. TLR9 responds to unmethylated CpG motif in bacterial and viral DNA [3], [4]. TLR4 is essential in the respective recognition of lipopolysaccharide (LPS) [4], lipoteichoic acid [5] and some other substrates [6], [7], [8]. A number of microbial substrates are known for TLR7 and TLR8 [8], [9], [10].

The main TLR-mediated immune response pathway, which is common for all TLRs, is Myeloid differentiation primary response gene 88 (MyD88)-dependent activation of Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (NF-kB) and c-Jun, transcription regulators of number of chemokines and cytokines responsible for cellular immune response. The main steps of NF-kB activation involve MyD88/ Interleukin-1 receptor-associated kinases (IRAK)/ TNF receptor-associated factor 6 (TRAF6)/ Mitogen-activated protein kinase kinase kinase 14 (NIK)/ Inhibitor of kappa light polypeptide gene enhancer in B-cells (IKK)/ NF-kB signal transduction [1]. C-Jun activation proceeds throw MyD88/ IRAK/ TRAF6/ Mitogen-activated protein kinase kinase kinase 7 interacting protein 1 (TAB)/ Mitogen-activated protein kinase kinase kinase 7 (TAK) cascade [4], [11]. TLR family members can induce autophagy through direct activation of Beclin 1 by MyD88 [12].

Besides MyD88, some TLRs use alternative adaptor proteins to induce NF-kB and c-Jun activation, such as Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) [4], [13]. Certain types of TLRs (for example, TLR3 and TLR4) demonstrate also other response pathways, which are specific for them.

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