Interleukin-6 induction by Helicobacter pylori in human macrophages is dependent on phagocytosis
Stefan Odenbreit1, Stefan Linder, Bettina Gebert-Vogl
1Max von Pettenkofer-Institute for Hygiene und Medical Microbiology, Ludwig-Maximilians-University, Pettenkoferstrasse 9a, D-80336 Munich, Germany. odenbreit@mvp.uni-muenchen.de
Background:
The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection.
Materials And Methods:
We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated.
Results:
IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 10(3)- to 10(4)-fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior.
Conclusions:
From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria.
Insights
Helicobacter pylori infection stimulates interleukin-6 (IL-6) production primarily in macrophages, requiring bacterial uptake. This highlights macrophages as key players in the gastric immune response to H. pylori.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Helicobacter pylori colonization elevates proinflammatory cytokines like IL-6 in the gastric mucosa.
- Understanding IL-6 stimulation mechanisms in phagocytes during H. pylori infection is crucial.
Purpose of the Study:
- To investigate the mechanisms of IL-6 stimulation in phagocytes following H. pylori infection.
- To identify the specific phagocyte types and bacterial components involved in IL-6 induction.
Main Methods:
- Assessed IL-6 secretion from murine and human phagocytes (granulocytes, monocytes, macrophages).
- Evaluated the impact of bacterial viability, phagocytosis, and subcellular fractions of H. pylori.
- Investigated the role of actin-dependent processes and Toll-like receptor 4 (TLR4) signaling.
Main Results:
- Human macrophages showed high IL-6 responsiveness to H. pylori and E. coli.
- IL-6 induction by H. pylori was dependent on actin-dependent processes and bacterial uptake.
- H. pylori membrane fractions were most active; its LPS had significantly lower activity than E. coli LPS, suggesting limited TLR4 involvement.
Conclusions:
- Macrophages are a major source of IL-6 in the gastric mucosa during H. pylori infection.
- IL-6 induction by H. pylori is a complex process involving bacterial uptake and degradation.
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