Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis

Abstract

Background CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis. Objectives To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with sepsis. Study Design A cohort of CMV-seropositive critically ill patients with sepsis due to bloodstream infection underwent weekly testing for CMV viremia. Blood samples to evaluate mRNA levels of genes encoding CASP1, ASC, NLRP1, NLRP3, and NLRP12 were collected at the time of enrollment. Clinical outcomes were assessed at 30 days or until death/discharge from ICU. Results CMV viremia was documented in 27.5% (8/29) of the patients, a median of 7 days after the onset of bacteremia. Patients with sepsis who developed CMV viremia had higher CASP1 although this was not statistically significant (relative mean 3.6 vs 1.8, p=0.13). Development of high grade CMV viremia however, was significantly associated with CASP1; septic patients who developed high grade CMV viremia had significantly higher CASP1 than all other patients (relative mean 5.5 vs 1.8, p=0.016). Conclusions These data document a possible involvement of inflammasomes in the pathogenesis of CMV. Regulating the host immune response by agents that target these genes may have implications for improving CMV-related outcomes in these patients.

Neutrophil pyroptosis: new perspectives on sepsis

“…At present, there are still few studies on the upstream molecules of pyroptosis in sepsis. A published study reveals an association of NLRP3 and Caspase-1 mRNA levels with severity of sepsis caused by cytomegalovirus (CMV) [126]. Another study suggested that caspase-1 is a potential marker for predicting the development of sepsis after severe trauma [127].…”

Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients

“…Effective assembly of the NLRP3 inflammasome complex and subsequent release of IL-1 β requires the components to be fully available intracellularly [ 15 ]. Whole-blood assays by Singh et al revealed enhanced NLRP3 mRNA levels in patients with septic shock that correlated with severity of the illness [ 41 ]. Nonetheless, the contribution of other cells than monocytes to the NLRP3 mRNA levels has to be taken into account, and additionally, the study population was rather small ( n = 29) [ 41 ].…”

“…Whole-blood assays by Singh et al revealed enhanced NLRP3 mRNA levels in patients with septic shock that correlated with severity of the illness [ 41 ]. Nonetheless, the contribution of other cells than monocytes to the NLRP3 mRNA levels has to be taken into account, and additionally, the study population was rather small ( n = 29) [ 41 ]. Another interesting work by a German group investigated inflammasome modulation in human monocytes after cardiopulmonal resuscitation (CPR) [ 42 ].…”

Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease

“…Thus, the nascent iOPN protein does not include signal sequence and stays in the cytoplasm (Shinohara et al, 2008). However, it appears that the Spp1 signal sequence transcript is somehow essential for initiating alternative translation (Inoue and Shinohara, 2011); thus, the complete removal of Spp1 signal sequence (45 nt) abolishes the production of not only sOPN but iOPN too (Kanayama et al, 2017;Shinohara et al, 2005Shinohara et al, , 2006Shinohara et al, , 2008Singh et al, 2017). Based on this information, we sought to generate sOPN alone by replacing the Spp1 signal sequence (45 nt) with the Il2 signal sequence (57 nt) (Figures 5A and S5A) (Sasada et al, 1988;Smith et al, 1985).…”