Innate Immunity Signaling Pathways: Links between Immunonutrition and Responses to Sepsis

Abstract

Septic infections in patients treated in intensive care units show the highest mortality rates. Despite advances in treatment methods, there is still no therapy available to efficiently reduce the excessive inflammatory response, which can increase the risk of multiple organ failure. One of the ways to discover new, more efficient treatment methods involves regulating the mechanisms of inflammatory response to a massive infection. Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns play a significant role in innate antibacterial and inflammatory responses. The regulatory impact of immunonutrition on TLR expression in septic patients seems to be a promising research direction. This paper presents the main mechanisms for the innate immune response to lipopolysaccharide, based on the research results for both TLR-dependent and independent signaling pathways. Special emphasis was put on the research results for the TLR-dependent immune response and the anti-bacterial/anti-inflammatory response after applying immunonutrition with increased concentrations of glutamine and unsaturated fatty acids.

Review paper Current views on the mechanisms of immune responses to trauma and infection

“…an appropriate nutritional treatment of immunonutrition type – agents blocking immune response by affecting the TLRs (e.g. Eritoran) [ 53 , 54 ]. The clinical usefulness of novel survival biomarkers and severity of infection has also been tested (e.g.…”

“…Endocan) [ 55 ]. Patients in metabolic stress after major trauma, surgery, or sepsis often require supply of a modified diet composition enriched with specific immune- modulating nutrients such as glutamine, arginine, omega-3 fatty acids, or nucleotides (Impact, Reconvan, Intestamin) [ 54 – 58 ]. Opinions on the use of immunonutrition in severely ill patients with post-traumatic sepsis, treated in the ICU, are still controversial.…”

Mitochondria: sensors and mediators of innate immune receptor signaling

“…Glutamine modulates the expression of TLR (independently of MyD88) by regulating the expression of TRIF (TIR-domain-containing adapter-inducing interferon-β)[36] (Fig.2). …”

Glutamine as an Immunonutrient

“…Even though the mechanisms by which nutrients improve certain disease states have not yet been clarified, reduction of morbidity and shorter length of stay in septic patients,5 as well as reduced wound infection in burn patients6 were demonstrated after enteral feeding of nutrients. Critically ill patients who received the immune formula had more rapid restoration of lymphocyte mitogenesis, reduction in infectious complications, and reduced mortality than those who did not 7.…”