Temporal changes of NF-κB signaling pathway genes in bacterial stimulated whole blood- a host mechanism associated with sepsis

Abstract

Bacterial sepsis affects both neonates and adults worldwide. There is no specific anti-sepsis treatment. Disease management mainly depends on early diagnosis. The gold standard blood culturing method is routinely practiced; it requires 24-48 h for confirmation. Understanding the disease mechanism may help in the early detection of sepsis. We studied the temporal change in NF-kB pathway genes in adult whole blood upon bacterial stimulations across time intervals (2-6 h). Four experimental conditions were investigated (1: Gram-positive, 2: Gram-negative, 3: Gram-positive + Gram-negative stimulated and compared with 4: un-stimulated group) to show host selection of canonical or non-canonical pathway against invading pathogens. Gene expression analysis showed significant variations (p < 0.5) in TLR2, TLR4, TRAF6, NIK, RelA, and RelB upon bacterial stimulants. Further, the correlation analysis showed the coherent behaviour of genes in selecting the canonical or non-canonical pathway. TLR2 sensed by gram-positive bacteria that immediately activates the canonical pathway through RelA, whereas other bacterial stimulants activate the non-canonical pathway via TLR4, NIK, and RelB. In addition, the inflammatory markers showed a significant increase in response to bacterial stimulants, suggesting the immediate activation of innate immunity. Overall, our results show the bacterial specific and time-dependent activation of the NF-kB pathway, which through a light towards the early detection of bacterial sepsis.

Keywords: Bacterial stimulation; Biomarkers; Gene expression; Inflammation; NF-kB pathway; Sepsis.