Association of a functional TNF variant with Plasmodium falciparum parasitaemia in a congolese population

Ngoc, Nguyen Huy; Baaklini, Sabrina; Koukouikila-Koussounda, Félix; Ndounga, Mathieu; Torres, Magali; Pradel, Lydie; Ntoumi, Francine; Rihet, Pascal

doi:10.1038/gene.2017.13

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…falciparum infection and/or clinical severity 21–24 . Most of the reports 22–24 have included TNF-α promoter polymorphisms, that are believed to affect mRNA expression and alter plasma levels of protein molecule. TNF-α (G-308A) mutants have been associated with susceptibility to P .…”

Section: Introductionmentioning

confidence: 99%

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TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area

Mahto

Tripathy

Meher

et al. 2019

Sci Rep

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Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine associated with autoimmune and infectious diseases. Importance of TNF-α in P . falciparum malaria and systemic lupus erythematosus (SLE) have been demonstrated. However, association of functional promoter variants with SLE and malaria is lacking in malaria endemic population. A total of 204 female SLE patients and 224 age and sex matched healthy controls were enrolled in the study. Three hundred fourteen P . falciparum infected patients with different clinical phenotypes were included. TNF-α polymorphisms (G-238A & G-308A) were genotyped by PCR-RFLP. Plasma levels of TNF-α was quantified by ELISA. Heterozygous mutants and minor alleles of TNF-α (G-238A and G-308A) polymorphisms were significantly higher in SLE patients compared to healthy controls and associated with development of lupus nephritis. In addition, both promoter variants were associated with severe P . falciparum malaria. SLE patients demonstrated higher levels of plasma TNF-α compared to healthy controls. TNF-α (G-238A and G-308A) variants were associated with higher plasma TNF-α. In conclusion, TNF-α (G-238A & G-308A) variants are associated with higher plasma TNF-α levels in SLE patients residing in malaria endemic areas and could be a contributing factor in the development of SLE and susceptibility to severe P . falciparum malaria.

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Section: Introductionmentioning

confidence: 99%

“…TNF-α (G-308A) mutants have been associated with susceptibility to P . falciparum infection 23 , higher levels of parasitaemia 22 and severe malaria 25 . However, an independent study on South-West Nigerian infected patients failed to demonstrate such association 24 .…”

Section: Introductionmentioning

confidence: 99%

TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area

Mahto

Tripathy

Meher

et al. 2019

Sci Rep

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“…Several TNF-α promoter single nucleotide polymorphisms (SNPs) that control gene expression or TNF production (89–92) are associated with control of parasitemia levels (92–95) and with increased anti- P. falciparum IgG levels (96). This suggests that TNF variants may play a role in the effectiveness of anti-parasite responses.…”

Section: Tumor Necrosis Factormentioning

confidence: 99%

Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective

Penha‐Gonçalves

2019

Front. Immunol.

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Despite significant progress in combating malaria in recent years the burden of severe disease and death due to Plasmodium infections remains a global public health concern. Only a fraction of infected people develops severe clinical syndromes motivating a longstanding search for genetic determinants of malaria severity. Strong genetic effects have been repeatedly ascribed to mutations and allelic variants of proteins expressed in red blood cells but the role of inflammatory response genes in disease pathogenesis has been difficult to discern. We revisited genetic evidence provided by inflammatory response genes that have been repeatedly associated to malaria, namely TNF, NOS2, IFNAR1, HMOX1, TLRs, CD36, and CD40LG. This highlighted specific genetic variants having opposing roles in the development of distinct malaria clinical outcomes and unveiled diverse levels of genetic heterogeneity that shaped the complex association landscape of inflammatory response genes with malaria. However, scrutinizing genetic effects of individual variants corroborates a pathogenesis model where pro-inflammatory genetic variants acting in early infection stages contribute to resolve infection but at later stages confer increased vulnerability to severe organ dysfunction driven by tissue inflammation. Human genetics studies are an invaluable tool to find genes and molecular pathways involved in the inflammatory response to malaria but their precise roles in disease pathogenesis are still unexploited. Genome editing in malaria experimental models and novel genotyping-by-sequencing techniques are promising approaches to delineate the relevance of inflammatory response gene variants in the natural history of infection thereby will offer new rational angles on adjuvant therapeutics for prevention and clinical management of severe malaria.

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“…Necroptosis is a form of regulated cell death generally manifested with a necrotic morphology, which is initiated by signals from the microenvironment that can be detected by specific death receptors, such as TNFR1 and FAS 28–33, or receptors for pathogen recognition, such as DAI, TLR3 and TLR4 34 35 36, 37. Engagement of death receptors triggers the activation of the receptor-interacting protein kinase 1 (RIPK1), which autophosphorylates and recruits RIPK3 through RIP homotypic interaction motif (RHIM) domains present on both kinases 38.…”

Section: Cell Death Modalitiesmentioning

confidence: 99%

Cell death pathologies: targeting death pathways and the immune system for cancer therapy

et al. 2018

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Alterations in the molecular mechanisms of cell death are a common feature of cancer. These alterations enable malignant cells to survive intrinsic death signalling leading to accumulation of genetic aberrations and helping them to cope with adverse conditions. Regulated cell death has historically been exclusively associated with classical apoptosis; however, increasing evidence indicates that several alternative mechanisms orchestrate multiple death pathways, such as ferroptosis, entosis, necroptosis and immunogenic cell death, each with distinct underlying molecular mechanisms. Although pharmacological targeting of cell death pathways has been the subject of intensive efforts in recent decades with a dominant focus on targeting apoptosis, the identification of these novel death pathways has opened additional venues for intervention in cancer cells and the immune system. In this mini-review, we cover some recent progress on major recently emerged cell death modalities, emphasizing their potential clinical and therapeutic implications. We also discuss the interplay between cell death and immune response, highlighting the potential of the combination of traditional anticancer therapy and immunocheckpoint blockade. While attempting to stimulate discussion and draw attention to the possible clinical impact of these more recently emerged cell death modalities, we also cover the major progress achieved in translating strategies for manipulation of apoptotic pathways into the clinic, focusing on the attempts to target the anti-apoptotic protein BCL-2 and the tumour suppressor p53.

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Association of a functional TNF variant with Plasmodium falciparum parasitaemia in a congolese population

Cited by 14 publications

References 36 publications

TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area

TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area

Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective

Cell death pathologies: targeting death pathways and the immune system for cancer therapy

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