MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia

Somuk, Battal Tahsin; Koç, Sema; Ateş, Ömer; Göktaş, Göksel; Soyalıç, Harun; Uysal, İsmail Önder; Gürbüzler, Levent; Sapmaz, Emrah; Sezer, Saime; Eyibilen, Ahmet

doi:10.1080/00016489.2016.1186835

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…Nramp1 was identified as part of the Bcg / Ity / Lsh locus in mice, which contributes to natural resistance against intracellular pathogens such as Mycobacteria, Leishmania , and Salmonella (Vidal et al, 1993, 1995). In humans, polymorphic variations of the nramp1 gene are linked to tuberculosis (Wu et al, 2013), leprosy (Abel et al, 1998) and oropharyngeal tularemia (Somuk et al, 2016). In contrast, isoforms of DMT-1 are responsible for transferrin-independent iron uptake (Canonne-Hergaux et al, 1999) or recycling via endosomes (Gruenheid et al, 1999; Touret et al, 2003), and have been associated with microcytic anemia (Fleming et al, 1997; Canonne-Hergaux et al, 2000) and neurodegeneration (Salazar et al, 2008).…”

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confidence: 99%

Nramp1 and NrampB Contribute to Resistance against Francisella in Dictyostelium

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Winther‐Larsen

et al. 2017

Front. Cell. Infect. Microbiol.

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The Francisella genus comprises highly pathogenic bacteria that can cause fatal disease in their vertebrate and invertebrate hosts including humans. In general, Francisella growth depends on iron availability, hence, iron homeostasis must be tightly regulated during Francisella infection. We used the system of the professional phagocyte Dictyostelium and the fish pathogen F. noatunensis subsp. noatunensis (F.n.n.) to investigate the role of the host cell iron transporters Nramp (natural resistance associated macrophage proteins) during Francisella infection. Like its mammalian ortholog, Dictyostelium Nramp1 transports iron from the phagosome into the cytosol, whereas the paralog NrampB is located on the contractile vacuole and controls, together with Nramp1, the cellular iron homeostasis. In Dictyostelium, Nramp1 localized to the F.n.n.-phagosome but disappeared from the compartment dependent on the presence of IglC, an established Francisella virulence factor. In the absence of Nramp transporters the bacteria translocated more efficiently from the phagosome into the host cell cytosol, its replicative niche. Increased escape rates coincided with increased proteolytic activity in bead-containing phagosomes indicating a role of the Nramp transporters for phagosomal maturation. In the nramp mutants, a higher bacterial load was observed in the replicative phase compared to wild-type host cells. Upon bacterial access to the cytosol of wt cells, mRNA levels of bacterial iron uptake factors were transiently upregulated. Decreased iron levels in the nramp mutants were compensated by a prolonged upregulation of the iron scavenging system. These results show that Nramps contribute to host cell immunity against Francisella infection by influencing the translocation efficiency from the phagosome to the cytosol but not by restricting access to nutritional iron in the cytosol.

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Section: Introductionmentioning

confidence: 99%

Nramp1 and NrampB Contribute to Resistance against Francisella in Dictyostelium

Brenz

Ohnezeit

Winther‐Larsen

et al. 2017

Front. Cell. Infect. Microbiol.

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Association of Hypomorphic P2X7 Receptor Genotype With Age

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Falzoni

Morieri

et al. 2020

Front. Mol. Neurosci.

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One of the main risk factors for brain diseases is aging. Recent studies have shown that aging is a progressive degenerative process associated with chronic low-level inflammation. The ATP-gated P2X7 receptor (P2X7R) plays an important role in inflammation and has been associated with different brain (e.g., Alzheimer's and Parkinson's) or other age-related (osteoporosis, arthritis, cancer) diseases. Several single nucleotide polymorphisms (SNPs) in the P2RX7 gene have been identified, including the loss-of-function 1513A>C and 1405A>G SNPs, and the gain-of-function 489C>T and 1068G>A SNPs. We carried out a literature analysis to verify an association between P2RX7 SNPs' frequency and age. In 34 worldwide eligible studies (11.858 subjects) no correlation between 1513CC genotype frequency and age emerged. On the contrary, analysis of European Caucasian cohorts (7.241 subjects) showed a significant increase in 1513CC frequency with age (P = 0.027). In agreement with these findings, analysis of two publicly available datasets, including USA Caucasian cohorts, unveiled an increased frequency of 1513CC and 489CC genotypes with age (P = 0.0055 and P = 0.0019, respectively). Thus, hypomorphic P2RX7 genotypes may be positively selected with age in European and North American Caucasian populations. We hypothesize that Caucasian individuals bearing an anti-inflammatory P2X7R phenotype and living in high-income countries may have a longer life expectancy.

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MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia

Cited by 2 publications

References 17 publications

Nramp1 and NrampB Contribute to Resistance against Francisella in Dictyostelium

Nramp1 and NrampB Contribute to Resistance against Francisella in Dictyostelium

Association of Hypomorphic P2X7 Receptor Genotype With Age

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