Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases.
Giuseppe CastronovoAnn Maria ClementeAlberto AntonelliMarco Maria D'AndreaMichele TanturliEloisa PerissiSara PaccosiAstrid ParentiFederico CozzolinoGian Maria RossoliniMaria Gabriella TorciaPublished in: PloS one (2017)
ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1β gene expression through p38MAPK- and NF-κB-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.
Keyphrases
- dendritic cells
- klebsiella pneumoniae
- induced apoptosis
- inflammatory response
- escherichia coli
- multidrug resistant
- nlrp inflammasome
- gene expression
- cell cycle arrest
- immune response
- cell death
- endothelial cells
- signaling pathway
- oxidative stress
- healthcare
- lps induced
- sars cov
- innate immune
- endoplasmic reticulum stress
- bone marrow
- anti inflammatory
- drug resistant
- machine learning
- lipopolysaccharide induced
- cystic fibrosis
- cell proliferation
- acute myeloid leukemia
- diabetic rats
- acinetobacter baumannii
- high glucose
- toll like receptor
- dna binding
- drug induced