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

• Published in: Clinical and experimental immunology 2017-08, Vol.189 (2), p.232-240
• Main Authors: Esquerdo, K. F., Sharma, N. K., Brunialti, M. K. C., Baggio‐Zappia, G. L., Assunção, M., Azevedo, L. C. P., Bafi, A. T., Salomao, R.
• Format: Article
• Language: English
• Subjects: Activation analysis; Adult; Aged; Aged, 80 and over; Bacteria; Brazil; Case-Control Studies; Cell Line; Community-Acquired Infections - complications; Female; Gene Expression; Humans; Inflammasomes; Inflammasomes - genetics; Inflammation; Inflammatory response; Information processing; Intensive care units; Interleukin 1; Interleukin 18; Interleukin-18 - genetics; Interleukin-18 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; interleukin‐1beta; Leucine; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Nitric oxide; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Nod1 protein; Oligomerization; Original; Peripheral blood mononuclear cells; Polymerase chain reaction; Prospective Studies; Pyroptosis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sepsis; Sepsis - genetics; Signal Transduction; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Toll‐like receptor; Transcription activation; Transcriptome
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12971

Summary 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. The inflammasome has emerged as a key modulator of the immune response and has been related to the pathogenesis of inflammatory and infectious diseases through the release of pro‐inflammatory cytokines and pyroptic cell death. Genes involved in the activation of the NLR‐inflammasome cascades were substantially altered 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. Activation and inhibition intensity for representing functions were different in survivors and non‐survivors, as for production of reactive oxygen species, synthesis