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.
Highlights
Host innate immune response plays a crucial role in defending the organism against infection
This study investigated the activation of the caspase‐1 inflammasome during the acute phase of infection, by repeated measurement over time, in a cohort of patients with S. aureus bacteremia (SAB), all with methicillin‐ sensitive S. aureus
The messenger RNA (mRNA) expression of NLRP3, CASP1, and IL1B was altered in patients with SAB compared with healthy controls, indicating a modified priming state of the NLRP3 inflammasome during bacteremia
Summary
Host innate immune response plays a crucial role in defending the organism against infection. Pattern‐recognition receptors (PRRs), such as Toll‐like receptors (TLRs) and NOD‐like receptors (NLRs), are able to recognize a wide range of microbial components, known as pathogen‐associated molecular patterns (PAMPs), as well as sterile molecules of stress and danger, so‐called damage‐associated molecular patterns (DAMPs). PRRs act as a first line of defense against infections and host damage. While TLRs are membrane‐bound, NLRs act as intracellular sensors for pathogens and stress.[1,2]. Some NLRs oligomerize and assemble with the adaptor protein ASC (apoptosis‐associated speck‐like protein containing a CARD) and procaspase‐. 1 to form multiprotein complexes known as inflammasomes. The assembly mediates caspase‐1 activation, which subsequently cleaves the proinflammatory cytokines IL‐1β and IL‐18 into their active forms.[3–5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
