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Updated: Jul 3, 2026
Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
Selective activation of human intestinal mast cells by Escherichia coli hemolysin
Sigrid Krämer1, Gernot Sellge, Axel Lorentz
1Department of Nutritional Medicine and Immunology, University of Hohenheim, Stuttgart, Germany.
Abstract:
Mast cells (MCs) are recognized to play an important role in bacterial host defense in the murine system. In this study, we studied the interaction of human MCs, isolated from the intestine and purified to homogeneity, with different Escherichia coli and Shigella flexneri strains. We show that alpha-hemolysin (Hly)-producing E. coli strains induce the release of histamine, leukotrienes, and proinflammatory cytokines in intestinal MCs. In contrast, MCs were virtually unresponsive to S. flexneri and several Hly-negative E. coli strains, including the isogenic Hly-deficient mutants of Hly(+) strains. Hly(+) E. coli but not Hly(-) E. coli caused an increase in intracellular Ca(2+) levels. Blocking of extracellular Ca(2+) and of the calmodulin/calcineurin pathway by cyclosporin A inhibited the response to Hly(+) E. coli. Furthermore, inhibition of MAPKs p38 and ERK reduces activation of MCs by Hly(+) E. coli. In addition, using an ex vivo system, we directly record the histamine release by MCs located in the lamina propria after infection with Hly(+) E. coli. Our data indicate that human intestinal mast cells interact with selected Gram-negative bacteria, establish E. coli Hly as a factor regulating MC effector functions, and argue further for a role of human MCs in innate immunity.
Insights
Human intestinal mast cells (MCs) release histamine and cytokines when encountering alpha-hemolysin-producing E. coli. This highlights MCs' role in innate immunity and bacterial defense.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Mast cells (MCs) are crucial for bacterial host defense in mice.
- Understanding human MC responses to bacteria is vital for innate immunity research.
Purpose of the Study:
- To investigate the interaction between human intestinal MCs and pathogenic bacteria.
- To identify bacterial factors that modulate human MC effector functions.
Main Methods:
- Isolated and purified human intestinal MCs were challenged with Escherichia coli and Shigella flexneri strains.
- Intracellular calcium (Ca2+) levels, mediator release (histamine, leukotrienes, cytokines), and signaling pathways (calmodulin/calcineurin, MAPKs) were analyzed.
- An ex vivo system was used to observe MCs in the lamina propria.
Main Results:
- Alpha-hemolysin (Hly)-producing E. coli induced significant histamine, leukotriene, and cytokine release from human MCs.
- MCs showed minimal response to S. flexneri and Hly-negative E. coli strains.
- Hly(+) E. coli triggered an increase in intracellular Ca2+ levels, which was inhibited by blocking extracellular Ca2+ and the calmodulin/calcineurin pathway.
- Inhibition of MAPKs (p38 and ERK) reduced MC activation by Hly(+) E. coli.
- Direct histamine release from lamina propria MCs upon Hly(+) E. coli infection was observed ex vivo.
Conclusions:
- Human intestinal MCs respond specifically to Hly-producing E. coli.
- E. coli alpha-hemolysin is a key factor regulating human MC effector functions.
- These findings support a significant role for human MCs in innate immunity against Gram-negative bacteria.
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