MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum

Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-β1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-β1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-β1, inhibition of ERK phosphorylation increased TGF-β1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-β1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine

Climate, human behaviour or environment: individual-based modelling of Campylobacter seasonality and strategies to reduce disease burden

Acknowledgements: We thank colleagues within the Modelling, Evidence and Policy Research Group for useful feedback on this manuscript. Competing interests: The authors declare that they have no competing interests. Availability of data and materials: The R code used in this research is available at https://gitlab.com/rasanderson/campylobacter-microsimulation; it is platform independent, R version 3.3.0 and above. Funding: This research was funded by Medical Research Council Grant, Natural Environment Research Council, Economic and Social Research Council, Biotechnology and Biological Sciences Research Council, and the Food Standards Agency through the Environmental and Social Ecology of Human Infectious Diseases Initiative (Sources, seasonality, transmission and control: Campylobacter and human behaviour in a changing environment (ENIGMA); Grant Reference G1100799-1). PRH, SJO’B, and IRL are funded in part by the NIHR Health Protection Research Unit in Gastrointestinal Infection, at the University of Liverpool. PRH and IRL are also funded in part by the NIHR Health Protection Research Unit in Emergency Preparedness and Response, at King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.Peer reviewedPublisher PD

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe