Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors

Abstract

Inflammasome signalling induces the processing and secretion of interleukin (IL)-1β and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in São Paulo were included into the study. We performed a polymerase chain reaction (PCR) array encompassing 35 genes related to the nucleotide-binding oligomerization domain and leucine-rich repeat-containing (NLR)-inflammasome in peripheral blood mononuclear cells obtained at admission and after 7 days of follow-up. Eleven healthy volunteers were used as the reference group. Increased NLRC4 and NLRP3 and decreased nucleotide-binding oligomerization domain (NOD1), and NLRP1 expression was observed in septic patients compared to healthy individuals; the IL-1β and IL-18 expression levels were also high in the patients. The gene expression changes followed the same patterns in surviving and non-surviving patients, with higher magnitudes observed in non-survivors. Functional analyses revealed, however, that activation and inhibition intensity for representing functions were different in survivors and non-survivors, as for production of reactive oxygen species, synthesis of nitric oxide and for the control of bacterial infections. Our results showed that the genes involved in the activation of the NLR-inflammasome cascades were altered substantially in septic patients, with a higher number of altered genes and a higher intensity in the disturbance of gene expression found among patients dying of sepsis.

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

“…Pyroptosis is an inflammatory form of programmed cell death. In general, pyroptosis protects multicellular host organisms against invasive pathogenic bacteria and microbial infections; however, it also causes sepsis and septic shock when overactivated ( Figure 1 ) [ 15 , 21 – 23 ]. In the 20th century, the discovery of Toll-like receptor- (TLR-) 4 was a key landmark for understanding innate- and specific-immune responses in infectious diseases, especially in sepsis.…”

Function of aquaporins in sepsis: a systematic review

“…It can be found in macrophages and neutrophil granulocytes and can recognize pathogens like bacteria. The inflammasome inter alia consists of NLR family pyrin domain containing 3 (NLRP3) which is up-regulated in sepsis [ 26 ]. Activation of NLRP3 inflammasome causes interleukin 1 beta (IL-1β) release.…”

Machine Learning Identifies Complicated Sepsis Course and Subsequent Mortality Based on 20 Genes in Peripheral Blood Immune Cells at 24 Hours post ICU admission

“…Phospholipase ( PLC ) proteins are mainly responsible for metabolizing inositol lipids and recent studies have shown that impairment of lipid metabolism is one of the major changes among patients with sepsis secondary to hospital-acquired pneumonia (49) . Finally, the NLR Family Pyrin Domain Containing 1 ( NLRP1 ) gene, which is one of the many genes responsible for the activation of the NLR-inflammasome cascades was found to be significantly altered among septic patients in a recent study (50) .…”