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Probiotic bacterial strains differentially modulate macrophage cytokine production in a strain-dependent and cell

N Habil1, W Al-Murrani, J Beal

  • 1School of Biomedical and Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom.

Beneficial Microbes
|December 8, 2011
PubMed

Insights

Heat-killed and secreted probiotic proteins differentially affect gut macrophage subsets. Probiotic interventions require a cautious approach for mucosal inflammation due to subset-specific immune responses.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Gut mucosal macrophages are crucial for immune responses, distinguishing between pathogens and beneficial microbes.
  • Macrophage polarization into M1 (inflammatory) and M2 (homeostatic) subsets is influenced by the tissue environment.
  • Probiotics can modulate macrophage function, but outcomes vary depending on the specific macrophage subset involved.

Purpose of the Study:

  • To investigate the immunomodulatory effects of heat-killed (HK) probiotic bacteria and their secreted proteins (SP) on M1 and M2 macrophage subsets.
  • To analyze the subset-specific regulation of inflammatory markers TNFα, IL-6, and NFκB activity.

Main Methods:

  • Utilized a THP-1 monocyte cell line model to generate CD14high (M1) and CD14low (M2) macrophages.
  • Stimulated macrophage subsets with enteropathic lipopolysaccharides in the presence or absence of HK probiotics or SP.
  • Measured cytokine expression via ELISA and NFκB activity using a reporter assay.

Main Results:

  • HK probiotics suppressed TNFα in CD14low M2 macrophages but augmented it in CD14high M1 macrophages.
  • SPs augmented TNFα in CD14high M1s while generally suppressing it in other subtypes.
  • Both HK and SPs suppressed IL-6 in M2 macrophages, with differential regulation in M1 subsets.
  • NFκB activation did not consistently parallel TNFα and IL-6 regulation, suggesting NFκB-independent mechanisms.

Conclusions:

  • Heat-killed and secreted probiotic components differentially regulate macrophage cytokines in a subset-dependent manner.
  • Probiotic bacteria appear to exert regulatory effects on TNFα and IL-6 independently of NFκB activation.
  • A cautious approach is recommended for probiotic use in managing mucosal inflammation due to varied subset-specific effects.

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