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Updated: Jul 15, 2026
Neutrophil Extracellular Traps: How to Generate and Visualize Them
Published on: February 24, 2010
Modulation of neutrophil extracellular traps release by Klebsiella pneumoniae
Federico Birnberg-Weiss1, Luis A Castillo1, Jose R Pittaluga1
1Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental (IMEX)-CONICET/Academia Nacional de Medicina, CABA, Argentina.
Abstract:
One of the main bactericidal mechanisms of polymorphonuclear neutrophils (PMN) is the release of neutrophil extracellular traps (NETs), which capture and destroy pathogens. Klebsiella pneumoniae (Kpn) producer of carbapenemase (KPC) and belonging to the sequence type 258 (ST258), is a hyper epidemic clone that causes a large number of infections worldwide associated with high persistence and mortality. It is necessary to investigate the interaction of Kpn KPC with the immune system to improve prevention and treatment of infections mediated by this bacterium. Based on the hypothesis that Kpn is able to subvert PMN-mediated death, the aim was to assess whether Kpn KPC ST258 could modulate the bactericidal response of PMN, focusing on NETs formation, compared to another opportunistic pathogen, as Escherichia coli (Eco). The results showed that the release of NETs was absent when PMN were challenged with Kpn KPC, while Eco was a strong inducer of NETosis. Moreover, Kpn KPC was able to inhibit NETosis induced by Eco. The inhibition of Kpn KPC-mediated NETs formation still occurred in spite of exogenous addition of hydrogen peroxide (H2 O2 ), did not involve bacterial-released soluble factors or cell wall components, and was dependent on bacterial viability. Moreover, when degranulation was investigated, we found that Kpn KPC affected only the mobilization of primary granules, which harbor the proteins with more potent bactericidal properties and those related to NETosis. In conclusion, Kpn KPC ST258 effectively managed to evade the PMN response by inhibiting the release of NETs, and primary granule mobilization.
Insights
Klebsiella pneumoniae (KPC) evades immune defenses by inhibiting neutrophil extracellular traps (NETs) formation. This carbapenem-resistant pathogen prevents PMN bactericidal activity, impacting infection treatment.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Neutrophil extracellular traps (NETs) are crucial for combating bacterial infections.
- Klebsiella pneumoniae carbapenemase (KPC) ST258 is a hyper-virulent pathogen associated with high mortality.
- Understanding KPC's interaction with the host immune system is vital for effective treatment strategies.
Purpose of the Study:
- To investigate the interaction between KPC ST258 and polymorphonuclear neutrophils (PMN).
- To determine if KPC ST258 can modulate PMN bactericidal responses, specifically NETs formation.
- To compare KPC ST258's effect on NETosis with that of Escherichia coli (Eco).
Main Methods:
- Challenging PMN with KPC ST258 and Eco to assess NETs release.
- Evaluating KPC ST258's ability to inhibit Eco-induced NETosis.
- Investigating the role of hydrogen peroxide, soluble factors, cell wall components, and bacterial viability in KPC's inhibition of NETosis.
- Analyzing PMN degranulation, focusing on primary granule mobilization.
Main Results:
- KPC ST258 significantly inhibited NETs formation, unlike Eco.
- KPC ST258 actively suppressed Eco-induced NETosis.
- The inhibition of NETosis by KPC was independent of soluble factors or cell wall components and required bacterial viability.
- KPC ST258 specifically impaired the mobilization of PMN primary granules, essential for bactericidal activity and NETosis.
Conclusions:
- KPC ST258 possesses a mechanism to evade the PMN bactericidal response by inhibiting NETs release.
- The evasion strategy involves the suppression of primary granule mobilization, crucial for effective pathogen clearance.
- These findings highlight a novel immune evasion tactic by KPC ST258, informing potential therapeutic interventions.
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