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Macrophage permissiveness for Legionella pneumophila growth modulated by iron
S J Gebran1, C Newton, Y Yamamoto
1Department of Medical Microbiology and Immunology, University of South Florida, Tampa 33612-4799.
Abstract:
We have investigated the modulation of iron in two populations of macrophages which differ in susceptibility to Legionella pneumophila intracellular proliferation. Previously, we reported that thioglycolate-elicited peritoneal macrophages obtained from the inbred A/J mouse strain readily support the intracellular growth of L. pneumophila, while resident macrophages from the same strain do not. In this study, we show that A/J elicited macrophages exhibit markedly higher expression of transferrin receptor and intracellular iron content than A/J resident macrophages. Furthermore, apotransferrin and desferrioxamine inhibited the intracellular proliferation of L. pneumophila in elicited macrophages, and this suppression was reversed by the additions of Fe-transferrin or ferric nitrilotriacetate. Fe-transferrin and ferric nitrilotriacetate did not further increase the intracellular proliferation of L. pneumophila in thioglycolate-elicited macrophages. However, ferric citrate and ferric nitrilotriacetate stimulated in a dose-dependent manner the growth of L. pneumophila in resident macrophages. Furthermore, equimolar concentrations of desferrioxamine reversed the stimulatory effect of iron in these resident cells. These data provide evidence supporting the hypothesis that differences in susceptibility to L. pneumophila growth between permissive elicited macrophages and nonpermissive resident macrophages from the A/J mouse strain are due to intracellular availability of iron.
Insights
Iron availability dictates macrophage susceptibility to Legionella pneumophila. Elicited macrophages, with higher iron, support bacterial growth, while resident macrophages, with lower iron, resist it, highlighting iron
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophages exhibit varying susceptibility to intracellular bacterial pathogens.
- Previous work showed A/J mouse strain elicited macrophages support Legionella pneumophila growth, unlike resident macrophages.
Purpose of the Study:
- To investigate the role of iron modulation in macrophage susceptibility to Legionella pneumophila.
- To determine if intracellular iron availability explains differential L. pneumophila proliferation in A/J macrophages.
Main Methods:
- Quantification of transferrin receptor expression and intracellular iron content in elicited versus resident macrophages.
- Assessment of L. pneumophila intracellular proliferation in response to iron chelators (apotransferrin, desferrioxamine) and iron donors (Fe-transferrin, ferric nitrilotriacetate, ferric citrate).
Main Results:
- A/J elicited macrophages showed higher transferrin receptor expression and intracellular iron than resident macrophages.
- Iron chelation inhibited L. pneumophila growth in elicited macrophages, reversible by iron repletion.
- Iron supplementation stimulated L. pneumophila growth in resident macrophages, inhibited by desferrioxamine.
Conclusions:
- Intracellular iron availability is a key determinant of macrophage permissiveness to Legionella pneumophila.
- Differential iron metabolism contributes to the distinct susceptibility of elicited versus resident macrophages to L. pneumophila infection.