Model-based Evaluation of Gene Expression Changes in Response to <i>Leishmania</i> Infection

Stamper, Brendan D.; Davis, Madison J.; Scott-Collins, Sean; Tran, Julie Thu A; Ton, Caryn; Simidyan, Agapi; Roberts, Sigrid C.

doi:10.1177/1177625019828350

Cited by 3 publications

(4 citation statements)

References 59 publications

(125 reference statements)

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“…These two reactive species appear to be the main molecules involved in immune defense of the host. Inhibition of nitric oxide and oxygen radicals may be escape mechanisms of the parasite for their survival [46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Kückelhaus

Aquino

Borges

et al. 2020

IJERPH

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Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.

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Section: Discussionmentioning

confidence: 99%

Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Kückelhaus

Aquino

Borges

et al. 2020

IJERPH

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“…Furthermore, variability among experimental conditions is another important factor that should be considered when interpreting the results of gene expression studies in Leishmania -infected murine macrophages. Differences in macrophage source (peritoneal-derived vs. bone marrow-derived), incubation time of macrophages with parasites and post-infection time points might all lead to conflicting results among studies [ 7 ]. For example, some discrepancies in the expression pattern of chemokine genes such as Ccl3 and Ccl4 , observed in BALB/c macrophages infected with either L .…”

Section: Discussionmentioning

confidence: 99%

“…The C57BL/6 and BALB/c mouse strains are among the host model systems commonly used in studies characterizing the immunopathogenesis of Leishmania species and antileishmanial effect of novel drug candidates [ 2 , 6 , 7 ]. C57BL/6 mice show resistance to Leishmania infections, due to a predominant Th1 cytokine response and M1 macrophage activation [ 4 , 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Gene expression patterns associated with Leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice

et al. 2021

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Leishmania parasites can trigger different host immune responses that result in varying levels of disease severity. The C57BL/6 and BALB/c mouse strains are among the host models commonly used for characterizing the immunopathogenesis of Leishmania species and the possible antileishmanial effect of novel drug candidates. C57BL/6 mice tend to be resistant to Leishmania infections, whereas BALB/c mice display a susceptible phenotype. Studying species-specific interactions between Leishmania parasites and different host systems is a key step to characterize and validate these models for in vivo studies. Here, we use RNA-Seq and differential expression analysis to characterize the transcriptomic profiles of C57BL/6 and BALB/c peritoneal-derived macrophages in response to Leishmania panamensis infection. We observed differences between BALB/c and C57BL/6 macrophages regarding pathways associated with lysosomal degradation, arginine metabolism and the regulation of cell cycle. We also observed differences in the expression of chemokine and cytokine genes associated with regulation of immune responses. In conclusion, infection with L. panamensis induced an inflammatory gene expression pattern in C57BL/6 macrophages that is more consistently associated with a classic macrophage M1 activation, whereas in BALB/c macrophages a gene expression pattern consistent with an intermediate inflammatory response was observed.

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“…All the variables mentioned above also affect transcriptional changes induced by other intracellular trypanosomes, as Leishmania (different infection models, the source and origin of the macrophages, parasite species, levels of infectivity, MOI, the used technology, data analysis, and interaction and analyzed times of infection) (Ashwin et al, 2018;Stamper et al, 2019) and probably they will also affect the transcriptional host changes caused by any intracellular microorganism.…”

Section: Are Transcriptomic Experiments Comparable To Each Other?mentioning

confidence: 99%

Transcriptional Studies on Trypanosoma cruzi – Host Cell Interactions: A Complex Puzzle of Variables

Libisch

Rego

Robello

2021

Front. Cell. Infect. Microbiol.

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Chagas Disease, caused by the protozoan parasite Trypanosoma cruzi, affects nearly eight million people in the world. T. cruzi is a complex taxon represented by different strains with particular characteristics, and it has the ability to infect and interact with almost any nucleated cell. The T. cruzi-host cell interactions will trigger molecular signaling cascades in the host cell that will depend on the particular cell type and T. cruzi strain, and also on many different experimental variables. In this review we collect data from multiple transcriptomic and functional studies performed in different infection models, in order to highlight key differences between works that in our opinion should be addressed when comparing and discussing results. In particular, we focus on changes in the respiratory chain and oxidative phosphorylation of host cells in response to infection, which depends on the experimental model of T. cruzi infection. Finally, we also discuss host cell responses which reiterate independently of the strain, cell type and experimental conditions.

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Model-based Evaluation of Gene Expression Changes in Response to Leishmania Infection

Cited by 3 publications

References 59 publications

Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Gene expression patterns associated with Leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice

Transcriptional Studies on Trypanosoma cruzi – Host Cell Interactions: A Complex Puzzle of Variables

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