Modulation of the immune response by nematode secreted acetylcholinesterase revealed by heterologous expression in Trypanosoma musculi

Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

Compensatory growth responses to defoliation and light availability in two native Mexican woody plant species

Defoliation, often caused by herbivory, is a common cause of biomass loss for plants that can affect current and future growth and reproduction. There are three models that predict contrasting compensatory growth responses of plants to herbivory and resource availability: (1) Growth rate model, (2) Compensatory continuum hypothesis and (3) Limiting resource model. The predictions of these three models were tested on the tree Brosimum alicastrum and the liana Vitis tiliifolia. Seedlings were subjected to three levels of experimental defoliation (0%, 50% and 90% leaf removal) along a light resource gradient (1%, 9% and 65% of full sun). In both species, defoliation significantly increased leaf production rate and relative growth rate of leaf area, but not of biomass. Net assimilation rate was the strongest driver of biomass growth in both species, but leaf area ratio and specific leaf area were also important in B. alicastrum. Compensatory responses of leaf area growth in B. alicastrum were significantly greater in higher than lower light availability, consistent with the compensatory continuum hypothesis predictions, but in contrast to the growth rate model predictions. The limiting resource model offered an explanation for all possible experimental outcomes by directly considering the effects of environmental differences in resource availabilit

Detrimental cross-talk between sepsis and acute kidney injury: new pathogenic mechanisms, early biomarkers and targeted therapies

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901