IRF3 function and immunological gaps in sepsis

Abstract

Lipopolysaccharide (LPS) induces potent cell activation via Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD-2), often leading to septic death and cytokine storm. TLR4 signaling is diverted to the classical acute innate immune, inflammation-driving pathway in conjunction with the classical NF-κB pivot of MyD88, leading to epigenetic linkage shifts in nuclear pro-inflammatory transcription and chromatin structure-function; in addition, TLR4 signaling to the TIR domain-containing adapter-induced IFN-β (TRIF) apparatus and to nuclear pivots that signal the association of interferons alpha and beta (IFN-α and IFN-β) with acute inflammation, often coupled with oxidants favor inhibition or resistance to tissue injury. Although the immune response to LPS, which causes sepsis, has been clarified in this manner, there are still many current gaps in sepsis immunology to reduce mortality. Recently, selective agonists and inhibitors of LPS signals have been reported, and there are scattered reports on LPS tolerance and control of sepsis development. In particular, IRF3 signaling has been reported to be involved not only in sepsis but also in increased pathogen clearance associated with changes in the gut microbiota. Here, we summarize the LPS recognition system, main findings related to the IRF3, and finally immunological gaps in sepsis.

Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling

“…This was accomplished by immunohistochemical determination of NFκB and NOX2 expression in neuroanatomical areas of the RVLM. NFκB is a pivotal transcription factor that predicts sepsis severity and Frontiers in Pharmacology frontiersin.org 10 Frontiers in Pharmacology frontiersin.org mortality and induces a variety of downstream proinflammatory effectors (Barnes and Karin, 1997;Böhrer et al, 1997;Arnalich et al, 2000;Abraham, 2003;Basak and Akashi-Takamura, 2024). NOX2 is a superoxide generating enzyme that positively relates to NFκB signaling and to the oxidative burst featured during sepsis (Ouyang et al, 2024).…”

Table3.XLSX

“…This was accomplished by immunohistochemical determination of NFκB and NOX2 expression in neuroanatomical areas of the RVLM. NFκB is a pivotal transcription factor that predicts sepsis severity and Frontiers in Pharmacology frontiersin.org 10 Frontiers in Pharmacology frontiersin.org mortality and induces a variety of downstream proinflammatory effectors (Barnes and Karin, 1997;Böhrer et al, 1997;Arnalich et al, 2000;Abraham, 2003;Basak and Akashi-Takamura, 2024). NOX2 is a superoxide generating enzyme that positively relates to NFκB signaling and to the oxidative burst featured during sepsis (Ouyang et al, 2024).…”

Table1.XLSX

“…This was accomplished by immunohistochemical determination of NFκB and NOX2 expression in neuroanatomical areas of the RVLM. NFκB is a pivotal transcription factor that predicts sepsis severity and Frontiers in Pharmacology frontiersin.org 10 Frontiers in Pharmacology frontiersin.org mortality and induces a variety of downstream proinflammatory effectors (Barnes and Karin, 1997;Böhrer et al, 1997;Arnalich et al, 2000;Abraham, 2003;Basak and Akashi-Takamura, 2024). NOX2 is a superoxide generating enzyme that positively relates to NFκB signaling and to the oxidative burst featured during sepsis (Ouyang et al, 2024).…”