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Cunnington A.J.,London School of Hygiene and Tropical Medicine | De Souza J.B.,London School of Hygiene and Tropical Medicine | De Souza J.B.,University College London | Walther M.,Medical Research Council Laboratories | Riley E.M.,London School of Hygiene and Tropical Medicine
Nature Medicine | Year: 2012

In sub-Saharan Africa, invasive nontyphoid Salmonella (NTS) infection is a common and often fatal complication of Plasmodium falciparum infection. Induction of heme oxygenase-1 (HO-1) mediates tolerance to the cytotoxic effects of heme during malarial hemolysis but might impair resistance to NTS by limiting production of bactericidal reactive oxygen species. We show that co-infection of mice with Plasmodium yoelii 17XNL (Py17XNL) and Salmonella enterica serovar Typhimurium 12023 (Salmonella typhimurium) causes acute, fatal bacteremia with high bacterial load, features reproduced by phenylhydrazine- induced hemolysis or hemin administration. S. typhimurium localized predominantly in granulocytes. Py17XNL, phenylhydrazine and hemin caused premature mobilization of granulocytes from bone marrow with a quantitative defect in the oxidative burst. Inhibition of HO by tin protoporphyrin abrogated the impairment of resistance to S. typhimurium by hemolysis. Thus, a mechanism of tolerance to one infection, malaria, impairs resistance to another, NTS. Furthermore, HO inhibitors may be useful adjunctive therapy for NTS infection in the context of hemolysis. © 2012 Nature America, Inc. All rights reserved.

Finney O.C.,Medical Research Council Laboratories | Finney O.C.,London School of Hygiene and Tropical Medicine | Finney O.C.,Seattle Biomedical Research Institute | Riley E.M.,London School of Hygiene and Tropical Medicine | Walther M.,Medical Research Council Laboratories
European Journal of Immunology | Year: 2010

Regulatory T cells (Treg) play crucial roles in regulating autoimmune responses and immunity to tumors and infectious diseases. However, numerous subpopulations of Treg are now being described and the utility of various Treg markers is being reassessed. Here we report the results of a detailed phenotypic comparison of two supposedly regulatory human T-cell populations, namely CD4+FOXP3+ T cells and CD4+CD25hi T cells. We find that CD4+FOXP3+ cells are extremely heterogeneous with respect to CD25 expression and that FOXP3+ and CD25hi CD4+ T cells differ in their expression of chemokine receptors (CCR), CD95 and Bcl-2, suggestive of distinct migration characteristics and susceptibility to apoptosis. Further, we propose that CD25 expression should be regarded as an activation marker rather than as a defining marker of Treg. Lastly, CD4+FOXP3+ T cells activated in vitro with malaria antigen expressed the highest levels of CCR4 and CD95, and the lowest levels of CCR7, indicating that they are most likely generated from effector memory cells during an immune response and rapidly succumb to apoptosis at the end of the response. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Lemoine M.,Medical Research Council Laboratories | Thursz M.,Imperial College London | Njie R.,Medical Research Council Laboratories | Dusheiko G.,University College London
Liver International | Year: 2014

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries. © 2013 John Wiley & Sons A/S.

Nweneka C.V.,Medical Research Council Laboratories | Prentice A.M.,Medical Research Council Laboratories | Prentice A.M.,London School of Hygiene and Tropical Medicine
BMC Gastroenterology | Year: 2011

Background: The nature of the association between ghrelin, an orexigenic hormone produced mainly in the stomach, and Helicobacter pylori (H pylori), a bacterium that colonises the stomach, is still controversial. We examined available evidence to determine whether an association exists between the two; and if one exists, in what direction.Methods: We reviewed original English language studies on humans reporting circulating ghrelin levels in H pylori infected and un-infected participants; and circulating ghrelin levels before and after H pylori eradication. Meta-analyses were conducted for eligible studies by combining study specific estimates using the inverse variance method with weighted average for continuous outcomes in a random effects model.Results: Seventeen out of 27 papers that reported ghrelin levels in H pylori positive and negative subjects found lower circulating ghrelin levels in H pylori positive subjects; while 10 found no difference. A meta-analysis of 19 studies with a total of 1801 participants showed a significantly higher circulating ghrelin concentration in H pylori negative participants than in H pylori positive participants (Effect estimate (95%CI) = -0.48 (-0.60, -0.36)). However, eradicating H pylori did not have any significant effect on circulating ghrelin levels (Effect estimate (95% CI) = 0.08 (-0.33, 0.16); Test for overall effect: Z = 0.67 (P = 0.5)).Conclusions: We conclude that circulating ghrelin levels are lower in H pylori infected people compared to those not infected; but the relationship between circulating ghrelin and eradication of H pylori is more complex. © 2011 Nweneka and Prentice; licensee BioMed Central Ltd.

Peterson K.,Medical Research Council Laboratories | Drame D.,Medical Research Council Laboratories
Sexually Transmitted Infections | Year: 2010

A woman presenting to an STI/HIV clinic in The Gambia with T vaginalis and a history of a digital vaginal 'exam' by a traditional healer implies non-sexual transmission of trichomonas between patients and reinforces the role of practitioner hygiene in preventing spread of infections.

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