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

Ahn, Danielle; Peñaloza, Hernán F.; Wang, Zheng; Wickersham, Matthew; Parker, Dane; Patel, Purvi; Koller, Antonius; Chen, Emily I.; Bueno, Susan M.; Uhlemann, Anne‐Catrin; Prince, Alice

doi:10.1172/jci.insight.89704

Cited by 56 publications

(114 citation statements)

References 53 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Cohen¹,

Pelletier²,

Cheng³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

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

Cohen¹,

Pelletier²,

Cheng³

et al. 2017

JCI Insight

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“…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.…”

Section: K Pneumoniae Resistance To Phagocytic Killingmentioning

confidence: 99%

“…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].…”

Section: K Pneumoniae Resistance To Phagocytic Killingmentioning

confidence: 99%

“…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].…”

Section: K Pneumoniae Resistance To Phagocytic Killingmentioning

confidence: 99%

“…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.…”

Section: K Pneumoniae Resistance To Phagocytic Killingmentioning

confidence: 99%

See 2 more Smart Citations

Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

Riquelme¹,

Ahn²,

Prince³

2018

J Innate Immun

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Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.

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The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study

Peñaloza

Álvarez

Muñoz‐Durango

et al. 2018

Journal of Leukocyte Biology

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An effective pathogen has the ability to evade the immune response. The strategies used to achieve this may be based on the direct action of virulence factors or on the induction of host factors. Myeloid‐derived suppressor cells (MDSCs) are immune cells with an incredible ability to suppress the inflammatory response, which makes them excellent targets to be exploited by pathogenic bacteria, viruses, or parasites. In this review, we describe the origin and suppressive mechanisms of MDSCs, as well as their role in chronic bacterial, viral, and parasitic infections, where their expansion seems to be essential in the chronicity of the disease. We also analyze the disadvantages of current MDSC depletion strategies and the different in vitro generation methods, which can be useful tools for the deeper study of these cells in the context of microbial infections.

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

Cited by 56 publications

References 53 publications

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

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

<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 role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study

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