The Nrf2 pathway is required for intracellular replication of<i>Toxoplasma gondii</i>in activated macrophages

Zhang, Zhaoxia; Chen, Yuntong; Cao, Shinuo; Yang, Xiuqin; Jia, Honglin

doi:10.1111/pim.12621

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…The capacity of ES to reduce LPS -induced inflammation when lacking Nrf2 was impaired, suggesting that anti-inflammatory role of ES may be primarily involved in the Nrf2 pathway. It has been also reported that T. gondii can balance the oxidative stress of IFN-γ and TNF-α –stimulated macropahges ( 40 ). In addition, we not only showed that Nrf2 participated in the development of T. spiralis ES -induced M2, but also verified that Nrf2 KO macrophage induced by T. spiralis ES failed to attenuate the severity of colitis and produced lower levels of IL-10 in vivo , suggesting that Nrf2 KO macrophages treated by ES did not exert their anti-inflammatory effects on colitis.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 98%

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

et al. 2021

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“…Nrf2-mediated anti-inflammatory response is thought to be ROS-dependent, although a recent report showed a direct inhibitory effect of Nrf2 on the recruitment of RNA polymerase II, preventing the transcription of genes coding for the proinflammatory cytokines IL-1β, IL-6 [9,10]. Furthermore, activation of Nrf2 signaling pathway in phagocytic cells improved their anti-viral and anti-bacterial functions [11][12][13]. Based on the literature, we selected 4 pharmacological compounds, found to modulate Nrf2 signaling, with anti-inflammatory properties: sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of 4 natural and chemical activators of Nrf2 on inflammation, oxidative stress, macrophage polarization, and bactericidal activity in an in vitro macrophage infection model

Ali¹,

Bonay²,

Vanhee³

et al. 2020

PLoS ONE

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Inflammation plays a crucial role in the defense response of the innate immune system against pathogen infection. In this study, we selected 4 compounds for their potential or proven anti-inflammatory and/or anti-microbial properties to test on our in vitro model of bacteria-infected THP-1-derived macrophages. We first compared the capacity of sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) to induce the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of the antioxidant, anti-inflammatory response pathways. Next, we performed a comparative evaluation of the antioxidant and anti-inflammatory efficacies of the 4 selected compounds. THP-1-derived macrophages and LPS-stimulated macrophages were treated with each compound and expression levels of genes coding for inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified by RT-qPCR. Moreover, expression levels of genes coding for M1 (IL-23, CCR7, IL-1β, IL-6, and TNF-α) and M2 (PPARγ, MRC1, CCL22, and IL-10) markers were determined in classicallyactivated M1 macrophages treated with each compound. Finally, the effects of each compound on the intracellular bacterial survival of gram-negative E. coli and gram-positive S. aureus in THP-1-derived macrophages and PBMC-derived macrophages were examined. Our data confirmed the anti-inflammatory and antioxidant effects of SFN, WG, and DMF on LPS-stimulated THP-1-derived macrophages. In addition, SFN or WG treatment of classically-activated THP-1-derived macrophages reduced expression levels of M1 marker genes, while SFN or DMF treatment upregulated the M2 marker gene MRC1. This decrease in expression of M1 marker genes may be correlated with the decrease in intracellular S. aureus load in SFN-or DMF-treated macrophages. Interestingly, an increase in intracellular survival of E. coli in SFN-treated THP-1-derived macrophages that was not observed in PBMC-derived macrophages. Conversely, OTZ exhibited pro-oxidant and proinflammatory properties, and affected intracellular survival of E. coli in THP-1-derived macrophages.

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“…The authors demonstrated that activation occurs in a p62-dependent manner. Activation of NRF2 was shown to be crucial for parasite growth [55]. Moreover, infection with Leishmania was also shown to activate the NRF2 pathway as NRF2-deficient cells were shown to exhibit decreased parasite load [56].…”

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confidence: 99%

Plasmodium berghei-Mediated NRF2 Activation in Infected Hepatocytes Enhances Parasite Survival

Bindschedler

Schmuckli‐Maurer

Wacker

et al. 2022

Cellular Microbiology

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The protozoan parasite Plasmodium, causative agent of malaria, initially invades and develops in hepatocytes where it resides in a parasitophorous vacuole (PV). A single invaded parasite develops into thousands of daughter parasites. Survival of the host cell is crucial for successful completion of liver stage development. Nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a transcription factor known to induce transcription of cytoprotective genes when activated. Here we show that NRF2 is activated in Plasmodium berghei-infected hepatocytes. We observed that this NRF2 activation depends on PV membrane resident p62 recruiting KEAP1, the negative regulator of NRF2. Disrupting the NRF2 gene results in reduced parasite survival, indicating that NRF2 signaling is an important event for parasite development in hepatocytes. Together, our observations uncovered a novel mechanism of how Plasmodium parasites ensure host cell survival during liver stage development.

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The Nrf2 pathway is required for intracellular replication ofToxoplasma gondiiin activated macrophages

Cited by 7 publications

References 31 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

Comparative effectiveness of 4 natural and chemical activators of Nrf2 on inflammation, oxidative stress, macrophage polarization, and bactericidal activity in an in vitro macrophage infection model

Plasmodium berghei-Mediated NRF2 Activation in Infected Hepatocytes Enhances Parasite Survival

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