Exploring reduced macrophage cell toxicity of hypervirulent Klebsiella pneumoniae compared to classical Klebsiella pneumoniae

Microbiol Res. 2024 Jan:278:127515. doi: 10.1016/j.micres.2023.127515. Epub 2023 Oct 11.

Abstract

Bacterial pneumoniae caused by Klebsiella pneumoniae (Kp) is a major concern due to the prevalence of multiple antibiotic-resistant strains, which limit treatment options and increase mortality rates. Patients with Kp infections often experience an uncontrolled immune response in the lungs, leading to excessive inflammation and elevated levels of proinflammatory cytokines. This study aimed to investigate the cytotoxicity, the inflammatory cytokine response, and the longevity of intracellular bacterial load in RAW 264.7 macrophages, infected with two different Kp strains - cKP (HKU1: Classical Kp) and HvKP (17ZR101: Hypervirulent Kp). This study found that after infecting macrophages with cKP and HvKP, the internalization rate was faster and the intracellular cKP load was higher than that of HvKP. Additionally, the number of intracellular Kp was correlated with the presence of M1 macrophage polarization marker CD86 and expressions of proinflammatory cytokines. Interestingly, the expression of these proinflammatory cytokines was significantly higher in cKP-infected macrophages than in HvKP-infected macrophages. Thus, a higher intracellular cKP load is suggested to play a significant role in causing more proinflammatory cytokines and killing macrophages compared to HvKP infection. This finding highlights the importance of understanding the mechanisms behind Kp infections and developing effective treatment strategies.

Keywords: Cytotoxicity; Klebsiella pneumoniae; M1 macrophage polarization; Macrophages; Proinflammatory cytokines.

MeSH terms

  • Anti-Bacterial Agents
  • Cytokines
  • Humans
  • Klebsiella Infections* / epidemiology
  • Klebsiella pneumoniae*
  • Macrophages

Substances

  • Anti-Bacterial Agents
  • Cytokines