One host defense mechanism that involves activation of an innate immune response following exposure to the external environment is the production of defensins. For instance in epithelial cells, hBD-2 and hBD-3 are expressed as a result of induction by bacteria, candida and inflammatory cytokines such as TNF-α and IL-1β.
One of the best characterized pathways in the defensin signal transduction pathway is the activation of the Toll like receptors (TLR´s). Toll-like receptors are a transmembrane receptor family that plays a pivotal role in the modulation of immune response by recognizing pathogen-associated molecular patterns.
This recognition subsequently stimulates a sequence of signaling mechanisms, resulting ultimately in the production of various cytokines that serve as a link between innate and specific immune mechanisms.
TLR-2 and TLR-4 are the best defined members of the TLR superfamily. TLR-4 recognizes lipopolysaccharides in Gram-negative bacteria, whereas TLR-2 plays a major role in the recognition of various bacterial components such as lipoteichoic acid, lipoproteins and peptide glycans.
The TLR receptors are most abundantly expressed in myelomonocytic subpopulation of leukocytes and the activation of the TLR subsequently leads to potent anti-inflammatory effect by down-regulating the mRNA expression of pro-inflammatory cytokines including IL-α, IL-1β, IL-6 and TNF-α.