Abstract
BackgroundSalmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. Given that the inflammasomes play an essential role in resisting bacterial infection, Salmonella has evolved various strategies to regulate activation of the inflammasome, most of which largely remain unclear.ResultsA transposon mutant library in SE strain C50336 was screened for the identification of the potential factors that regulate inflammasome activation. We found that T3SS-associated genes invC, prgH, and spaN were required for inflammasome activation in vitro. Interestingly, C50336 strains with deletion or overexpression of Dam were both defective in activation of caspase-1, secretion of IL-1β and phosphorylation of c-Jun N-terminal kinase (Jnk). Transcriptome sequencing (RNA-seq) results showed that most of the differentially expressed genes and enriched KEGG pathways between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups overlapped, which includes multiple signaling pathways related to the inflammasome. C50336Δdam and C50336::dam were both found to be defective in suppressing the expression of several anti-inflammasome factors. Moreover, overexpression of Dam in macrophages by lentiviral infection could specifically enhance the activation of NLRP3 inflammasome independently via promoting the Jnk pathway.ConclusionsThese data indicated that Dam was essential for modulating inflammasome activation during SE infection, there were complex and dynamic interplays between Dam and the inflammasome under different conditions. New insights were provided about the battle between SE and host innate immunological mechanisms.
Highlights
Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection
J774A.1 cells were pre-treated with LPS (1 μg/ mL, 5 h) and infected with wild type (WT) strain C50336 and dam, invC, hilD, prgH, and spaN gene deletion mutants at an MOI of 20 for 4 h, uninfected cells was used as a negative control (Blank). a
The production of IL-1β c and IL-6 d in supernatants were examined via enzymelinked immunosorbent assay (ELISA). ***p < 0.001 for one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison test indicate significant findings in comparison with cells infected with WT strain C50336
Summary
Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. The ability of Salmonella to invade host cells is dependent upon the Salmonella pathogenicity island-1 (SPI-1)-encoded type III secretion system (T3SS) which injects effector proteins into the host cell cytosol to modulate cellular responses, while the SPI-2 T3SS subsequently translocates virulence proteins to subvert the bactericidal properties of macrophages and create a specialized Salmonella-containing vacuole (SCV) for replication [8]. This special intracellular lifestyle exposes Salmonella to detection by inflammasomes, which have been identified as playing an essential role in the innate immune response against Salmonella infection [9]
Sign-in/Register to view highlights & summary 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.
