An investigation into the effects of metabolic disturbance on monocyte inflammatory response and regulation

The presence of chronic inflammation is associated with increased nutrient availability during obesity or type 2 diabetes which contributes to the development of complications such as atherosclerosis, stroke and myocardial infarction. The link between increased nutrient availability and inflammatory response remains poorly understood. The functioning of monocytes, the primary instigators of the inflammatory response was assessed in response to obesity and increased glucose availability. Monocyte microRNA expression was assessed in obese individuals prior to and up to one year after bariatric surgery. A number of microRNAs were identified to be dysregulated in obesity, some of which have previously been linked to the regulation of monocyte inflammatory responses including the microRNAs 146a-5p and 424-5p. Weight loss in response to bariatric surgery lead to the reversal of microRNA changes towards control values. In vitro treatments of THP-1 monocytes with high concentrations of D-glucose resulted in decreased intracellular NAD+:NADH ratio, decreased SIRT1 deacetylase activity and increased P65 acetylation. However the increased osmotic concentration inhibited LPS induced inflammatory response and TNFα mRNA expression. In vitro treatment of primary human monocytes with increased concentrations of D-glucose resulted in increased secretion of a number of inflammatory cytokines and increased expression of TNFα mRNA. Treatment also resulted in decreased intracellular NAD+:NADH ratio and increased binding of acetylated P65 to the TNFα promoter region. In vitro treatments of primary monocytes also replicated the altered expression of the microRNAs 146a-5p and miR-424-5p, as seen in obese individuals. In conclusion a number of changes in monocyte function were observed in response to obesity and treatment with high concentrations of D-glucose. These may lead to the dysregulation of inflammatory responses contributing to the development of co-morbidities

Complement as a regulator of adaptive immunity

International audienceThe complement system is an ancient and evolutionarily conserved effector system comprising in mammals over 50 circulating and membrane bound proteins. Complement has long been described as belonging to the innate immune system; however, a number of recent studies have demonstrated its key role in the modulation of the adaptive immune response. This review does not set out to be an exhaustive list of the numerous interactions of the many complement components with adaptive immunity; rather, we will focus more precisely on the role of some complement molecules in the regulation of antigen presenting cells, as well as on their direct effect on the activation of the core adaptive immune cells, B and T lymphocytes. Recent reports on the local production and activation of complement proteins also suggest a major role in the control of effector responses. The crucial role of complement in adaptive immunity is further highlighted by several examples of dysregulation of these pathways in human diseases

The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

BACKGROUND: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. METHODS: A prospective observational study of HCW's in Scotland (UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2/12/2020) post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection. RESULTS: A total of 2063 health and social care workers were recruited for this study. At enrolment 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85–6.16, p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCW who were previously antibody negative and one symptomatic RT-PCR positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (HR 0.15, 95% CI 0.06 to 0.35, p=0.026). CONCLUSION: HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response which was 85% effective in protecting against re-infection with SARS-CoV-2

The anthelmintic drug Praziquantel promotes human Tr1 differentiation

International audienc