The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

Vivarini, Áislan de Carvalho; Lopes, Ulisses Gazos

doi:10.3389/fcimb.2019.00453

Cited by 16 publications

(10 citation statements)

References 75 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nrf2 positively regulates transcription of genes having antioxidant effects ( 37 ). Nrf2 expression and activation occurs during the initial contact of some Leishmania species with cells, increasing the amount of gene products associated with M2 macrophage characteristics ( 38 ). We also showed that Nrf2 may be involved in altering the phenotype of ES –induced macrophages.…”

Section: Discussionmentioning

confidence: 99%

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

et al. 2021

View full text Add to dashboard Cite

Trichinella spiralis induced alternative activated macrophages (M2), leading to protect against Crohn’s disease, known as Th1 –related inflammation, which enhances oxidative stress in the host. However, the relationship of oxidative stress and T. spiralis –mediated immune response is still unknown. In our study, we showed that nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcription factor in antioxidant, participated in M2 polarization induced by T. spiralis muscle larval excretory/secretory (ES) products in vitro. ES –treated M2 were injected intravenously after TNBS challenge and we demonstrated that ES-M could alleviate the severity of the colitis in mice. Adoptive transfer of ES –treated M2 decreased the level of IFN-γ and increased the levels of IL-4 and IL-10 in vivo. However, the capacity of ES –treated Nrf2 KO macrophages to treat colitis was dramatically impaired. ES –treated Nrf2 KO macrophages was insufficient to result in the elevated levels of IL-4 and IL-10. These findings indicate that Nrf2 was required for M2 polarization induced by T. spiralis ES to alleviate colitis in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nrf2, as a key redox-sensitive transcription factor responses for the progression of bacterial infection ( 27 , 28 ), by modulating diverse phase 2 detoxifying enzymes and various stress-responsive proteins. Under unstressed conditions, the interaction between Nrf2 and Keap1 causes continual ubiquitination and degradation of Nrf2 in the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection

Zhou²,

Xu³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundListeria monocytogenes (L. monocytogenes), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of L. monocytogenes-host interactions.MethodsHemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis. Histological analysis, ELISA assay and biochemistry detection were conducted to assess in vivo efficacy of candidates.ResultsIn the present study, natural terpenoid atractylodin was characterized as an alternative drug candidate for the treatment of L. monocytogenes by the regulation of LLO function and host Nrf2/NLRP3 signaling pathway. Notably, in vivo infection model by L. monocytogenes also highlighted that atractylodin treatment provided effective therapeutic benefits, as evidenced by decreased bacterial burden and diminished inflammation. Congruently, the survival rate of L. monocytogenes-infection mice increased significantly from 10.0% to 40.0% by atractylodin treatment.ConclusionCollectively, our study showed for the first time that atractylodin has tremendous potential to attenuate L. monocytogenes pathogenicity by blocking LLO pore formation and mediating the suppression of inflammation and oxidative stress, providing a promising therapeutic strategy and broadening the applications of atractylodin against L. monocytogenes infection.

show abstract

“…In addition, PTEN is also inactivated during the oxidative stress process by ROS ( Leslie et al, 2003 ) and NO production in humans ( Kwak et al, 2010 ). Low PTEN can lead to the activation of Nrf2 ( Taguchi et al, 2014 ) that is responsible to modulate the antioxidative pathway and favors infection by L. infantum ( Vivarini and Lopes, 2020 ). Our findings suggest that L. infantum regulates PTEN in CanL.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis

et al. 2023

View full text Add to dashboard Cite

Canine Visceral leishmaniasis (CanL) poses a severe public health threat in several countries. Disease progression depends on the degree of immune response suppression. MicroRNAs (miRs) modulate mRNA translation into proteins and regulate various cellular functions and pathways associated with immune responses. MiR-21 and miR-148a can alter the parasite load and M1 macrophages are the principal cells in dogs’ leishmanicidal activity. A previous study found increased miR-21 and miR-148a in splenic leukocytes (SL) of dogs with CanL using microarray analysis and in silico analysis identified PTEN pathway targets. PTEN is involved in the immune regulation of macrophages. We measured PTEN and the production of reactive oxygen species (ROS) and nitric oxide (NO) before and after transfection SLs of dogs with CanL with mimic and inhibition of miR-21 and miR-148a. PTEN levels increased, NO and ROS decreased in SLs from dogs with CanL. Inhibition of miRNA-21 resulted in PTEN increase; in contrast, PTEN decreased after miR-148a inhibition. Nitrite (NO2) levels increased after transfection with miR-21 inhibitor but were decreased with miR-148a inhibitor. The increase in miR-21 promoted a reduction in ROS and NO levels, but miR-148a inhibition increased NO and reduced ROS. These findings suggest that miR-21 and miR-148a can participate in immune response in CanL, affecting PTEN, NO, and ROS levels.

show abstract

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

Cited by 16 publications

References 75 publications

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection

MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis

Contact Info

Product

Resources

About