Abstract
Microbe-derived factors trigger innate immune responses through the production of inflammatory mediators, including pentraxin 3 (PTX3). PTX3 is a soluble pattern recognition molecule that stimulates the clearance of clinically important bacterial pathogens such as Pseudomonas aeruginosa. However, the P. aeruginosa factors responsible for the production of PTX3 have not been elucidated. In this study, we found that P. aeruginosa DnaK, a homolog of heat shock protein 70, induced PTX3 production. Induction was mediated by intracellular signals transmitted through the Toll-like receptor 4 (TLR4) signaling pathway. Following receptor engagement, the stimulatory signals were relayed initially through the nuclear factor kappa B (NF-κB) signaling pathway and subsequently by extracellular signal-regulated kinases (ERK), which are mitogen-activated protein kinases. However, ERK activation was negatively controlled by NF-κB, implying the existence of negative crosstalk between the NF-κB and the ERK pathways. These data suggest that P. aeruginosa DnaK acts as a pathogen-associated molecular pattern to trigger modulation of host defense responses via production of PTX3.
Highlights
Innate immune responses play essential roles in defending against microbial infections in animals (e.g., infections by avian influenza, swine influenza, Aspergillus, pathogenicEscherichia coli (E. coli), Shigella, and Pseudomonas aeruginosa (P. aeruginosa)) [1,2,3,4,5,6,7]
P. aeruginosa-Derived DnaK Increases the Production of pentraxin 3 (PTX3)
Soluble forms of pattern recognition molecule PTX3 are critical for recognition of conserved molecular patterns present in pathogens, thereby building innate immunity against infection
Summary
Innate immune responses play essential roles in defending against microbial infections in animals (e.g., infections by avian influenza, swine influenza, Aspergillus, pathogenicEscherichia coli (E. coli), Shigella, and Pseudomonas aeruginosa (P. aeruginosa)) [1,2,3,4,5,6,7]. PRMs are critical for the recognition of conserved microbial moieties expressed on the surface or released by pathogens They are divided into two groups based on their localization: cell-associated receptors (e.g., Toll-like receptors (TLRs), Nod-like receptors, and RIG-like receptors) and fluid-phase molecules (e.g., complement compartments, mannose-binding lectin, and pentraxins (PTXs)). In addition to their recognition effect, fluid-phase PRMs contribute to innate immunity by influencing the regulation of complement activation, opsonization of pathogens, and regulation of inflammation [8]. PTX3 forms a 340 kDa octamer composed of two tetramers linked together by covalent bonds This evolutionarily conserved structure allows for the recognition of diverse bacterial, fungal, and viral pathogens, such as P. aeruginosa, Shigella flexneri (S. flexneri), uropathogenic
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.
