Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma

Bellmann‐Weiler, Rosa; Martinz, Verena; Kurz, Katharina; Engl, Sabine; Feistritzer, Clemens; Fuchs, Dietmar; Rupp, Jan; Paldanius, Mika; Weiss, Günter

doi:10.1016/j.imbio.2010.05.021

Cited by 27 publications

(29 citation statements)

References 64 publications

(64 reference statements)

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“…10 It has been suggested that C. pneumoniae infection of macrophages is often in a persistent form, which explains the observed refractory behavior of C. pneumoniae infection to antibiotic treatment in cells of monocyte-macrophage line. 11,12 Thus, new treatments are needed to fight the chlamydial infections and avoid the treatment failures.…”

Section: Introductionmentioning

confidence: 99%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

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Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca 2+ ) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca 2+ modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca 2+ modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca 2+ modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 lM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 lM), whereas 10 lM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 lM and 100 lM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 lM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca 2+ modulators potentiate the antichlamydial effects of the phenolic compounds.

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Section: Introductionmentioning

confidence: 99%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

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“…This might imply that the population of macrophages in atherosclerotic lesions is more heterogeneous than it is currently thought. CD68 [2,14,17,56,65] . The presence of C. pneumoniae in these cell types was detected in human arterial wall as well [7,9,15,18,25,65,66] .…”

Section: Discussionmentioning

confidence: 99%

“…However, the course of infection might be different in different cell types in atherosclerotic lesions. A recent study [65] revealed that the infectious cycle of C. pneumoniae behaves differently between monocytic and endothelial cells. It has been suggested that, while the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells, indicating that endothelial cells are a preferred environment for C. pneumoniae [65] .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study [65] revealed that the infectious cycle of C. pneumoniae behaves differently between monocytic and endothelial cells. It has been suggested that, while the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells, indicating that endothelial cells are a preferred environment for C. pneumoniae [65] . Bellmann-Weiler et al [65] showed that nutritive factors such as iron have subtle effects on C. pneumoniae biology in endothelial but not monocytic cells and that C. pneumoniae responds differently to immune stimulation by IFN-␥ , modulation of iron availability and restriction of tryptophan in endothelial versus monocytic cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that, while the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells, indicating that endothelial cells are a preferred environment for C. pneumoniae [65] . Bellmann-Weiler et al [65] showed that nutritive factors such as iron have subtle effects on C. pneumoniae biology in endothelial but not monocytic cells and that C. pneumoniae responds differently to immune stimulation by IFN-␥ , modulation of iron availability and restriction of tryptophan in endothelial versus monocytic cells. Bellmann-Weiler et al [65] suggested that monocytes may not be a good environment for the multiplication of C. pneumoniae but rather act as a shuttle for C. pneumoniae in the circulation to reach endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Decreased Expression of Liver X Receptor-α in Macrophages Infected with <i>Chlamydia pneumoniae</i> in Human Atherosclerotic Arteries in situ

Bobryshev¹,

Orekhov²,

Killingsworth³

et al. 2011

J Innate Immun

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In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells.

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Lipocalin‐2 ensures host defense against Salmonella Typhimurium by controlling macrophage iron homeostasis and immune response

et al. 2015

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Lipocalin-2 (Lcn2) is an innate immune peptide with pleiotropic effects. Lcn2 binds iron-laden bacterial siderophores, chemo-attracts neutrophils and has immunomodulatory and apoptosis-regulating effects. In this study we show that upon infection with Salmonella enterica serovar Typhimurium, Lcn2 promotes iron export from Salmonella-infected macrophages, which reduces cellular iron content and enhances the generation of pro-inflammatory cytokines. Lcn2 represses IL-10 production while augmenting Nos2, TNF-α and IL-6 expression. Lcn2-/- macrophages have elevated IL-10 levels as a consequence of increased iron content. The crucial role of Lcn-2/IL-10 interactions was further demonstrated by the greater ability of Lcn2-/- IL-10-/- macrophages and mice to control intracellular Salmonella proliferation in comparison to Lcn2-/- counterparts. Over-expression of the iron exporter ferroportin-1 in Lcn2-/- macrophages represses IL-10 and restores TNF-α and IL-6 production to the levels found in wild-type macrophages, so that killing and clearance of intracellular Salmonella is promoted. Our observations suggest that Lcn2 promotes host resistance to Salmonella Typhimurium infection by binding bacterial siderophores and suppressing IL-10 production, and that both functions are linked to its ability to shuttle iron from macrophages.

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Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma

Cited by 27 publications

References 64 publications

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

Decreased Expression of Liver X Receptor-α in Macrophages Infected with <i>Chlamydia pneumoniae</i> in Human Atherosclerotic Arteries in situ

Lipocalin‐2 ensures host defense against Salmonella Typhimurium by controlling macrophage iron homeostasis and immune response

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