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Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity
C E Alford1, T E King, P A Campbell
1Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Abstract:
It is not yet known what properties distinguish macrophages which can kill facultative intracellular bacteria, such as Listeria monocytogenes, from those which cannot. Listeria is an organism which requires iron for growth, yet macrophage listericidal mechanisms are also likely to be iron dependent. We show here that resident peritoneal macrophages and thioglycollate-elicited macrophages cannot kill listeria, but proteose peptone-elicited and FCS-elicited macrophages can. All these cell populations phagocytose listeria. Transferrin receptor expression is low on resident cells, intermediate on peptone- and FCS-elicited cells, and high on thioglycollate-elicited cells. Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate-elicited cells is high. Moreover, antibody to transferrin, which prevents it binding its receptor, inhibits listericidal macrophages from killing this bacterium. Finally, nonlistericidal cells with high transferrin receptor expression and high intracellular iron become listericidal if they are incubated with apotransferrin, an iron-free ligand which prevents iron uptake by cells. These data suggest that macrophages must have enough available intracellular iron to support listericidal mechanisms, but too much iron favors growth of the bacterium, which no longer can be killed by the macrophage.
Insights
Macrophages require sufficient intracellular iron to kill Listeria monocytogenes. However, excessive iron promotes bacterial growth, hindering macrophage-mediated killing. This highlights a critical balance for effective bacterial clearance.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages are crucial immune cells involved in clearing intracellular pathogens.
- The mechanisms by which macrophages kill bacteria like Listeria monocytogenes are not fully understood.
- Iron availability is known to be essential for both bacterial growth and macrophage function.
Purpose of the Study:
- To investigate the role of intracellular iron content and transferrin receptor expression in macrophage listericidal activity.
- To determine the optimal iron levels for macrophages to effectively kill Listeria monocytogenes.
Main Methods:
- Comparing listericidal activity of different macrophage populations (resident, thioglycollate-elicited, proteose peptone-elicited, FCS-elicited).
- Assessing transferrin receptor expression and intracellular iron content in these macrophage populations.
- Investigating the effect of anti-transferrin antibody and apotransferrin on macrophage listericidal capacity.
Main Results:
- Proteose peptone-elicited and FCS-elicited macrophages demonstrated listericidal activity, unlike resident and thioglycollate-elicited macrophages.
- Listericidal macrophages exhibited intermediate to high transferrin receptor expression and intracellular iron levels.
- Blocking iron uptake with apotransferrin rendered non-listericidal cells capable of killing Listeria.
Conclusions:
- Macrophage listericidal activity against Listeria monocytogenes is iron-dependent.
- An optimal intracellular iron concentration is necessary for effective bacterial killing.
- Excessive intracellular iron can impair macrophage listericidal function by promoting bacterial growth.