Malaria Pigment Hemozoin Impairs GM-CSF Receptor Expression and Function by 4-Hydroxynonenal

Skorokhod, Oleksii A.; Barrera, Valentina; Mandili, Giorgia; Costanza, Federica; Valente, Elena; Ulliers, Daniela; Schwarzer, Evelin

doi:10.3390/antiox10081259

Cited by 6 publications

(14 citation statements)

References 60 publications

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“…Natural HZ was prepared as previously described (14, 15). Briefly, 12 h after schizogony of synchronized FCR3 parasite cultures, the supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Lasaviciute,

Tariq,

Sugathan

et al. 2024

Preprint

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Hemozoin (HZ), the malaria pigment, is released together with the parasite during the blood stage of the disease, which is connected with the pro-inflammatory response to induce T-cells and B-cells. Co- infections with bacteria lead to a more severe disease progression and the underlying mechanisms are poorly understood. Here, we investigated the impact of HZ on the early response of monocyte-derived dendritic cells (moDC) to a common bacterial component, LPS. A short-term HZ exposure for two hours did not induce an inflammatory response, but it did alter the transcriptional response to LPS. In moDC co-exposed to HZ and LPS, the induction of HLR-DR and PD-L1 gene expression was reduced and associated with decreased binding of RELA compared to LPS-stimulated cells. These gene promoters recruited the silencing chromatin remodelling complex NuRD upon co-exposure, instead of the PBAF complex at the promoter in LPS-stimulated cells. Further, HZ maintained transcription of C-type lectin receptors associated to an immature DC phenotype, DC-SIGN (CD209) and macrophage mannose receptor (MMR/CD206). Here, activated RELA and IRF3 were recruited in a PBAF and NCBAF dependent manner. Upon LPS co-exposure, NuRD was replacing these complexes to allow for a reduced transcriptional level of these immature markers. The association of chromatin remodelling complexes did not alter the chromatin state at the promoters, which was changed during differentiation to DCs or even at an earlier point. In conclusion, HZ exposure primes specific gene promoters at an early time point, which results in a different transcriptional response and may also lead to a changed immune reaction to bacterial co-infections.

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“…Natural HZ was prepared as previously described (14, 15). Briefly, 12 h after schizogony of synchronized FCR3 parasite cultures, the supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Lasaviciute,

Tariq,

Sugathan

et al. 2024

Preprint

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“…That study showed involvement of CSF-2 in activation of granulocyte-macrophage hematopoiesis and resistance to P. chabaudi infection [ 83 ]. An explanation for the lack of differences in the levels of anemia in infected mice may stem from the action of the malarial pigment hemozoin, which impairs CSF-2 receptor expression and function [ 84 ]. However, Babesia spp.…”

Section: Phagocytosismentioning

confidence: 99%

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

Zygner

Gójska-Zygner²,

Norbury

2023

Pathogens

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Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite’s developmental stages only have a marginal role in contributing to a decreased red blood cell (RBC) count. The main cause of anemia in affected dogs is the immune response to the infection. This response includes antibody production, erythrophagocytosis, oxidative damage of RBCs, complement activation, and antibody-dependent cellular cytotoxicity. Moreover, both infected and uninfected erythrocytes are retained in the spleen and sequestered in micro-vessels. All these actions are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8. Additionally, imbalance between the actions of pro- and anti-inflammatory cytokines plays a role in patho-mechanisms leading to anemia in canine babesiosis. This article is a review of the studies on the pathogenesis of anemia in canine babesiosis and related diseases, such as bovine or murine babesiosis and human or murine malaria, and the role of pro-inflammatory cytokines and chemokines in the mechanisms leading to anemia in infected dogs.

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“…93,111,112 In these immune cells, the overload of lipid oxidation products HETEs and 4-hydroxynonenal (4-HNE) due to HZ was observed 92,93,113 and their contribution to immune imbalance in malaria is described. [114][115][116] Impaired HETEs' metabolism by CYPs may contribute to immunologically active HETEs accumulation and immune imbalance (Figure 4). Thus, any damage to CYP enzymes could perturb a balanced immune response to malaria, and studies of specific CYPs affected in malaria is crucial.…”

Section: P450 and Host Immunity In Malariamentioning

confidence: 99%

“…In malaria, HZ is engulfed directly by phagocytes or is accumulated after phagocytosis of parasitized erythrocytes containing HZ 93,111,112 . In these immune cells, the overload of lipid oxidation products HETEs and 4‐hydroxynonenal (4‐HNE) due to HZ was observed 92,93,113 and their contribution to immune imbalance in malaria is described 114–116 . Impaired HETEs' metabolism by CYPs may contribute to immunologically active HETEs accumulation and immune imbalance (Figure 4).…”

Section: Malariamentioning

confidence: 99%

The role of P450 enzymes in malaria and other vector‐borne infectious diseases

2023

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Vector‐borne infectious diseases are still an important global health problem. Malaria is the most important among them, mainly pediatric, life‐threatening disease. Malaria and other vector‐borne disorders caused by parasites, bacteria, and viruses have a strong impact on public health and significant economic costs. Most vector‐borne diseases could be prevented by vector control, with attention to the ecological and biodiversity conservation aspects. Chemical control with pesticides and insecticides is widely used as a measure of prevention although increasing resistance to insecticides is a serious issue in vector control. Metabolic resistance is the most common mechanism and poses a big challenge. Insect enzyme systems, including monooxygenase CYP P450 enzymes, are employed by vectors mainly to metabolize insecticides thus causing resistance. The discovery and application of natural specific inhibitors/blockers of vector P450 enzymes as synergists for commonly used pesticides will contribute to the “greening” of insecticides. Besides vector CYPs, host CYP enzymes could also be exploited to fight against vector‐borne diseases: using mostly their detoxifying properties and involvement in the immune response. Here, we review published research data on P450 enzymes from all players in vector‐borne infections, that is, pathogens, vectors, and hosts, regarding the potential role of CYPs in disease. We discuss strategies on how to exploit cytochromes P450 in vector‐borne disease control.

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Malaria Pigment Hemozoin Impairs GM-CSF Receptor Expression and Function by 4-Hydroxynonenal

Cited by 6 publications

References 60 publications

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

The role of P450 enzymes in malaria and other vector‐borne infectious diseases

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