Global cellular changes induced by Legionella pneumophila infection of bone marrow-derived macrophages

Fortier, Anne H.; Faucher, Sébastien P.; Diallo, Kanny; Gros, Philippe

doi:10.1016/j.imbio.2011.06.008

Cited by 13 publications

(17 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected increased expression of pro-inflammatory KC (protein and mRNA) and Il6 (mRNA) in WT BMMs and to a significantly lesser extent also in MyD88 -/- cells at 24 h post infection (p.i., Fig 1A and 1B). Additionally, we confirmed a reduction in Sesn1 mRNA levels upon infection as previously described [9], which was significantly stronger in WT BMMs than in MyD88 -/- BMMs at 24 h p.i. These established markers substantiated the pro-inflammatory macrophage phenotype that was expected to manifest after infection.…”

Section: Resultssupporting

confidence: 90%

“…Primer sequences were obtained from the PrimerBank database (https://pga.mgh.harvard.edu/primerbank/) or from the referenced publications. The following primers were used: Ntan1 (NM_010946, sense: , antisense: , PrimerBank ID 87299633c2), Cxcl1/Kc (NM_008176, sense: , antisense: , PrimerBank ID 229577225c1), Il6 (NM_031168, sense: , antisense: , PrimerBank ID 13624310c1), Sesn1 (NM_001162908, sense: , antisense: , [9]), Gapdh (NM_001289726.1, sense: ; antisense: , [10]). Commercial microRNA primers were purchased from Life Technologies.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1

et al. 2017

View full text Add to dashboard Cite

BackgroundLegionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. It is highly adapted to intracellular replication and manipulates host cell functions like vesicle trafficking and mRNA translation to its own advantage. However, it is still unknown to what extent microRNAs (miRNAs) are involved in the Legionella-host cell interaction.MethodsWT and MyD88-/- murine bone marrow-derived macrophages (BMM) were infected with L. pneumophila, the transcriptome was analyzed by high throughput qPCR array (microRNAs) and conventional qPCR (mRNAs), and mRNA-miRNA interaction was validated by luciferase assays with 3´-UTR mutations and western blot.ResultsL. pneumophila infection caused a pro-inflammatory reaction and significant miRNA changes in murine macrophages. In MyD88-/- cells, induction of inflammatory markers, such as Ccxl1/Kc, Il6 and miR-146a-5p was reduced. Induction of miR-125a-3p was completely abrogated in MyD88-/- cells. Target prediction analyses revealed N-terminal asparagine amidase 1 (NTAN1), a factor from the n-end rule pathway, to be a putative target of miR-125a-3p. This interaction could be confirmed by luciferase assay and western blot.ConclusionTaken together, we characterized the miRNA regulation in L. pneumophila infection with regard to MyD88 signaling and identified NTAN1 as a target of miR-125a-3p. This finding unravels a yet unknown feature of Legionella-host cell interaction, potentially relevant for new treatment options.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Moreover, constant stress and cellular senescence can exacerbate immune responses that lead to chronic inflammation, which results in disease progression because of changes in homeostatic set points (45). Although A/J mice have natural deficiencies of complement (C5a) and NOD (Naip5) genes involved in susceptibility to bacterial/fungal infection, recombinant congenic strains (46,47) have shown that these genes are controlled by additional factors and have little effect on the inflammatory-priming pathways highlighted in this study. In young A/J mice (and to a lesser degree BALB/c mice, but not B6 mice), RNA-Seq revealed an inflammatory-primed network characterized by increased expression of IFN gene products, such as Stat1 and its downstream effectors (23).…”

Section: Pathway Analysis Highlights Inflammatory Priming Coupled Witmentioning

confidence: 83%

Inflammatory priming predisposes mice to age-related retinal degeneration

Mustafi¹,

Maeda²,

Kohno³

et al. 2012

J. Clin. Invest.

View full text Add to dashboard Cite

Disruption of cellular processes affected by multiple genes and accumulation of numerous insults throughout life dictate the progression of age-related disorders, but their complex etiology is poorly understood. Postmitotic neurons, such as photoreceptor cells in the retina and epithelial cells in the adjacent retinal pigmented epithelium, are especially susceptible to cellular senescence, which contributes to age-related retinal degeneration (ARD). The multigenic and complex etiology of ARD in humans is reflected by the relative paucity of effective compounds for its early prevention and treatment. To understand the genetic differences that drive ARD pathogenesis, we studied A/J mice, which develop ARD more pronounced than that in other inbred mouse models. Although our investigation of consomic strains failed to identify a chromosome associated with the observed retinal deterioration, pathway analysis of RNA-Seq data from young mice prior to retinal pathological changes revealed that increased vulnerability to ARD in A/J mice was due to initially high levels of inflammatory factors and low levels of homeostatic neuroprotective factors. The genetic signatures of an uncompensated preinflammatory state and ARD progression identified here aid in understanding the susceptible genetic loci that underlie pathogenic mechanisms of age-associated disorders, including several human blinding diseases. IntroductionAge-related disorders arise from failure of tissue maintenance and repair pathways that are accelerated by certain inherited and acquired factors (1). Long-lived nondividing cells, such as neurons, have markedly reduced tolerance to damage (2), and thus exhibit the most pronounced age-related changes. Neuronal cells in the retina are an especially attractive model system to study this phenomenon, owing to their accessibility and wellunderstood physiology. Rod and cone photoreceptors are retinal neuronal cells that initiate visual perception, a function requiring a competent neighboring retinal pigmented epithelium (RPE) for their normal operation (3). In postmitotic cells such as these photoreceptor and RPE cells, cellular senescence can ensue when shed oxidized photoreceptor outer segments (POS) are inadequately phagocytosed and digested by the RPE. This results in accumulation of damaged proteins, formation of toxic metabolic byproducts, inflammatory cell invasion, and cell death. RPE cells are the most affected because, in addition to processing POS, they serve as the conduit between photoreceptors and the choroidal blood supply for metabolite exchange (4). Acquisition of senescence-associated pathology stimulates cells to secrete various factors that contribute to tissue dysfunction. Conversely, adequate clearance of such cells can delay the onset of age-related tissue pathology (5).Aging laboratory experimental animals are important models for studying age-related pathology, especially neurodegenerative disorders, which have been shown to be affected by their genetic backgrounds (6, 7). The A/J inbred mouse ...

show abstract

“…Legionella pneumophila was shown to regulate transcription of genes implicated in proliferation of human monocyte-derived macrophages and of bone marrow-derived macrophages3536. Furthermore, L. pneumophila modifies the host chromatin resulting in a repression of gene expression3738.…”

Section: Discussionmentioning

confidence: 99%

Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii

Mengue¹,

Régnacq²,

Aucher³

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Legionella pneumophila is a ubiquitous, pathogenic, Gram-negative bacterium responsible for legionellosis. Like many other amoeba-resistant microorganisms, L. pneumophila resists host clearance and multiplies inside the cell. Through its Dot/Icm type IV secretion system, the bacterium injects more than three hundred effectors that modulate host cell physiology in order to promote its own intracellular replication. Here we report that L. pneumophila prevents proliferation of its natural host Acanthamoeba castellanii. Infected amoebae could not undergo DNA replication and no cell division was observed. The Dot/Icm secretion system was necessary for L. pneumophila to prevent the eukaryotic proliferation. The absence of proliferation was associated with altered amoebal morphology and with a decrease of mRNA transcript levels of CDC2b, a putative regulator of the A. castellanii cell cycle. Complementation of CDC28-deficient Saccharomyces cerevisiae by the CDC2b cDNA was sufficient to restore proliferation of CDC28-deficient S. cerevisiae and suggests for the first time that CDC2b from A. castellanii could be functional and a bona fide cyclin-dependent kinase. Hence, our results reveal that L. pneumophila impairs proliferation of A. castellanii and this effect could involve the cell cycle protein CDC2b.

show abstract

Global cellular changes induced by Legionella pneumophila infection of bone marrow-derived macrophages

Cited by 13 publications

References 62 publications

microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1

microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1

Inflammatory priming predisposes mice to age-related retinal degeneration

Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii

Contact Info

Product

Resources

About