Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4

“…IL-17, via the epithelium, recruits neutrophils to the lung and polarizes them toward a PMN-I phenotype, making cells more capable of antimicrobial function than the alternative PMN-II cells, and increases the antimicrobial capacity of interstitial macrophages (26,41,42). This is made more relevant during infection with a pathogen, such as K. pneumoniae, some strains of which, including clinically relevant ST258 isolates, have been reported to exhibit enhanced evasion of neutrophil-mediated clearance (15,43). In the context of a K. pneumoniae infection, the OPK functionality of LPS-specific mAbs synergizes with the antimicrobial effects of IL-17 on neutrophil function.…”

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

“…The exact mechanism by which these CRKP isolates avoid intracellular killing, particularly by neutrophils, has yet to be elucidated. In vitro studies have established that ST258 isolates, in contrast to the KPPR1 strain, are resistant to neutrophil killing ex vivo [101, 102]. Differences in the production of respiratory burst and ROS generation [103, 104] have been observed; however, no specific bacterial genes have been identified that correlate with this phenotype.…”

“…Differences in the production of respiratory burst and ROS generation [103, 104] have been observed; however, no specific bacterial genes have been identified that correlate with this phenotype. The mechanisms appear to involve resistance to Ca 2+ -dependent killing [102]. It is clear that neutrophils and/or monocytes are critical to the host in clearance of ST258 isolates, as mice treated with anti-Ly6G antibodies have increased bacterial burden [102, 105].…”

“…The mechanisms appear to involve resistance to Ca 2+ -dependent killing [102]. It is clear that neutrophils and/or monocytes are critical to the host in clearance of ST258 isolates, as mice treated with anti-Ly6G antibodies have increased bacterial burden [102, 105]. One recent study utilized an anti-LPS-O-antigen antibody to increase opsonophagocytic killing capacity of neutrophils without loss of TLR4 signaling, likely from enhanced bacterial recognition by neutrophils [106].…”

“…One recent study utilized an anti-LPS-O-antigen antibody to increase opsonophagocytic killing capacity of neutrophils without loss of TLR4 signaling, likely from enhanced bacterial recognition by neutrophils [106]. However, this may not be universal as the ST258 isolates appear to be readily phagocytosed [87] but not killed [102], suggesting a mechanism by which intracellular killing processes are inhibited.…”