SWansea ImmunoMetabolismResearch Lab
Publications
Some of the latest publications from our group are linked below.
Endometriosis: how the condition may be linked to the immune system
Endometriosis is a debilitating condition which affects 10% of women worldwide. The condition can have a serious affect on a person’s quality of life, often causing a range of symptoms including chronic pain, fatigue and pain during sex.
The dynamic inflammatory profile of pregnancy can be monitored using a novel lipid-based mass spectrometry technique
The lipid environment changes throughout pregnancy both physiologically with emergent insulin resistance and pathologically e.g., gestational diabetes mellitus (GDM). Novel mass spectrometry (MS) techniques applied to minimally processed blood might lend themselves to monitoring changing lipid profiles to inform care decisions across pregnancy. In this study we use an intact-sandwich, MALDI-ToF MS method to identify phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) species and calculate their ratio as an indicator of inflammation. Plasma and sera were prepared from venous blood of non-pregnant women (aged 18–40) and pregnant women at 16 weeks, 28 weeks (including GDM-positive women), and 37+ weeks (term) of gestation alongside umbilical cord blood (UCB). Women with a normal menstrual cycle and age-matched men provided finger-prick derived capillary sera at 6 time-points over a month. Serum rather than plasma was preferable for PC/LPC measurement. As pregnancy progresses, an anti-inflammatory phenotype dominates the maternal circulation, evidenced by increasing PC/LPC ratio. In contrast, the PC/LPC ratio of UCB was aligned to that of non-pregnant donors. BMI had no significant effect on the PC/LPC ratio, but GDM-complicated pregnancies had significantly lower PC/LPC at 16 weeks of gestation. To further translate the use of the PC/LPC ratio clinically, the utility of finger-prick blood was evaluated; no significant difference between capillary versus venous serum was found and we revealed the PC/LPC ratio oscillates with the menstrual cycle. Overall, we show that the PC/LPC ratio can be measured simply in human serum and has the potential to be used as a time-efficient and less invasive biomarker of (mal)adaptative inflammation.
Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation
Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.
Potential protective effects of breast milk and amniotic fluid against novel coronavirus SARS-CoV-2 through decoy receptors
Infection of pregnant women during previous coronavirus-mediated pandemics, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), was associated with high rates of fetal and maternal demise. However, the characteristics of COVID-19 in pregnant and non-pregnant women are very similar, and while severe COVID-19 in pregnancy brings increased risk of preterm birth and intensive care admission,1 most pregnant women, be they symptomatic or asymptomatic for SARS-CoV-2 infection, do not experience severe complications in pregnancy.2 Similarly, cases of SARS-CoV-2 vertical transmission are rare and there is low risk of serious disease for the neonate.3 Understanding the mechanisms of resilience against severe COVID-19 in pregnant women and the newborn is critical to ensure ongoing vigilance in care and to provide insight into disease pathogenesis and therapeutic opportunities.
Angiotensin-converting enzyme 2 (ACE2), CD26, CD147, and neuropilin-1 (NRP-1) are some of the key molecules identified as contributing to the entry of coronaviruses such as SARS-CoV-2 into human cells.4 There is immense interest in these and viral entry facilitating proteases such as transmembrane serine protease 2 (TMPRSS2) as therapeutic targets for limiting infection. Soluble forms of viral entry receptors have been postulated to act as viral traps for SARS-CoV-2 by preventing interaction of the virus with membrane-bound forms.5 We predict that elevation of these at the maternal-fetal interface contributes to the lack of vertical transmission and limits severity of disease from SARS-CoV-2 infection in the fetus and neonate