Caspase‐1 inflammasome activity in patients with Staphylococcus aureus bacteremia

Abstract

The inflammasome is a multiprotein complex that mediates caspase‐1 activation with subsequent maturation of the proinflammatory cytokines IL‐1β and IL‐18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. This study therefore aimed to investigate NLRP3 inflammasome activity in 20 patients with S. aureus bacteremia (SAB), by repeated measurement during the first week of bacteremia, compared with controls. Caspase‐1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (fluorescent‐labeled inhibitor of caspase‐1), while IL‐1β and IL‐18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, messenger RNA (mRNA) expression of NLRP3, CASP1 (procaspase‐1), and IL1B (pro‐IL‐1β) was analyzed by quantitative PCR. We found induced caspase‐1 activity in innate immune cells with subsequent release of IL‐18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial interindividual variation in caspase‐1 activity between patients with SAB. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in SAB could provide support in the effort to optimize management and treatment of each individual patient.

Extracellular vesicles secreted by Giardia duodenalis regulate host cell innate immunity via TLR2 and NLRP3 inflammasome signaling pathways

“…NLRP3 has been deeply studied since it could recognize various bacteria, viruses, fungi, parasites and nigericin and uric acid crystals, etc. and involves in many intracellular pathogens induced disease, such as Staphylococcus aureus bacteremia [ 17 , 57 , 58 ]. However, limited research focus on the immune mechanisms mediated by the intracellular NLRs in extracellular pathogen of G .…”

Aggravated MRSA pneumonia secondary to influenza A virus infection is derived from decreased expression of IL‐1β

“…AMs limit the replication of pathogens and eliminate infections in the lungs by producing cytokines such as IL‐1β 35 . Numerous studies have identified the protective role of the NLRP3 inflammasome during IAV and MRSA infection via IL‐1β, which mediates inflammatory pathology and is associated with increased survival rate 24,36 . ‐ 38 …”

“…IAV, influenza A virus; MRSA, methicillin-resistant staphylococcus aureus; NLRP3, nucleotide-binding domain-like receptor protein 3; PBS, phosphate-buffered saline and MRSA infection via IL-1β, which mediates inflammatory pathology and is associated with increased survival rate. 24,[36][37][38] Severe MRSA pneumonia usually occurs as a result of prior viral infection. And it is prone to occur at 5 to 7 days after the initial IAV infection.…”

“…21 Research focused on the pathogenesis of S. aureus infection secondary to IAV has accumulated for these years. 9,14,18,[22][23][24][25][26][27][28][29] However, there is much less information available on MRSA pneumonia secondary to IAV infection. 30 Blyth et al 10 concluded that coinfection of IAV and bacteria synergistically aggravated inflammatory injury to the host.…”

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

“…On the other hand, excessive inflammasome activation, leading to exaggerated caspase-1 activation, IL-1β release, and pyroptosis, will cause severe cell and tissue damage and organ dysfunction, and ultimately death. So not surprisingly, patients with either too high or too low NLRP3 inflammasome signaling, as is the case for aged individuals, are potentially at higher risk of death [171]. Genetic or pharmacological inhibition of NLRP3 improves survival during polymicrobial sepsis or E. coli infection in mice [172,173].…”