Infection-induced innate antimicrobial response disorders: from signaling pathways and their modulation to selected biomarkers

Severe infections are a major public health problem responsible for about 40-65% of hospitalizations in intensive care units (ICU). The high mortality (30-50%) of persons diagnosed with severe infection is caused by largely unknown mechanisms of sepsis-induced immune system response. Severe infections with dynamic progress are accompanied with SIRS (systemic inflammatory reaction syndrome) and CARS (compensatory anti-inflammatory response syndrome), and require a biological treatment appropriate to the phase of immune response. The mechanisms responsible for severe infection related to immune system response particularly attract extensive interest of non-specific defense mechanisms, including signaling pathways of Toll-like receptors (mainly TLR4 and TLR2) that recognize distinct pathogen-associated molecular patterns (PAMP) and play a critical role in innate immune response. There are attempts of treatment, followed by blocking ligand binding with TLR or modulation of intracellular signaling pathways, to inhibit signal transduction. Moreover, researches regarding new and more efficient diagnostics biomarkers were mostly focused on indicators related to innate response to infection as well as connections of pro-inflammatory response with anti-inflammatory response. According to these studies, in case of ICU septic patients with high-risk of mortality, the solution for the problem will require mainly early immune and genetic diagnostics (e.g. cytokines, microRNA, cluster of differentiation-64 [CD64], triggering receptor expressed on myeloid cells-1 [TREM-1], and high mobility group box 1 protein [HMGB1]).